Today I fall into a strange problem, my app suddenly stop working on my USB plugged device. However it could run fine on other real devices and simulator devices.
The error dialog on screen is as usual: Unfortunately "your app name" has stopped.
To get the error messages, I run my app in debug mode and see this:
FATAL EXCEPTION: main
Process: com.yourapp.packagename, PID: 20036
java.lang.RuntimeException: Unable to instantiate application com.android.tools.fd.runtime.BootstrapApplication: java.lang.IllegalStateException: java.lang.ClassNotFoundException: android.support.multidex.MultiDexApplication
at android.app.LoadedApk.makeApplication(LoadedApk.java:676)
at android.app.ActivityThread.handleBindApplication(ActivityThread.java:6294)
at android.app.ActivityThread.access$1800(ActivityThread.java:222)
at android.app.ActivityThread$H.handleMessage(ActivityThread.java:1861)
at android.os.Handler.dispatchMessage(Handler.java:102)
at android.os.Looper.loop(Looper.java:158)
at android.app.ActivityThread.main(ActivityThread.java:7229)
at java.lang.reflect.Method.invoke(Native Method)
at com.android.internal.os.ZygoteInit$MethodAndArgsCaller.run(ZygoteInit.java:1230)
at com.android.internal.os.ZygoteInit.main(ZygoteInit.java:1120)
Caused by: java.lang.IllegalStateException: java.lang.ClassNotFoundException: android.support.multidex.MultiDexApplication
at com.android.tools.fd.runtime.BootstrapApplication.createRealApplication(BootstrapApplication.java:220)
at com.android.tools.fd.runtime.BootstrapApplication.attachBaseContext(BootstrapApplication.java:239)
at android.app.Application.attach(Application.java:211)
at android.app.Instrumentation.newApplication(Instrumentation.java:1020)
at android.app.Instrumentation.newApplication(Instrumentation.java:1004)
at android.app.LoadedApk.makeApplication(LoadedApk.java:666)
at android.app.ActivityThread.handleBindApplication(ActivityThread.java:6294)
at android.app.ActivityThread.access$1800(ActivityThread.java:222)
at android.app.ActivityThread$H.handleMessage(ActivityThread.java:1861)
at android.os.Handler.dispatchMessage(Handler.java:102)
at android.os.Looper.loop(Looper.java:158)
at android.app.ActivityThread.main(ActivityThread.java:7229)
at java.lang.reflect.Method.invoke(Native Method)
at com.android.internal.os.ZygoteInit$MethodAndArgsCaller.run(ZygoteInit.java:1230)
at com.android.internal.os.ZygoteInit.main(ZygoteInit.java:1120)
Caused by: java.lang.ClassNotFoundException: android.support.multidex.MultiDexApplication
at java.lang.Class.classForName(Native Method)
at java.lang.Class.forName(Class.java:324)
at java.lang.Class.forName(Class.java:285)
at com.android.tools.fd.runtime.BootstrapApplication.createRealApplication(BootstrapApplication.java:209)
at com.android.tools.fd.runtime.BootstrapApplication.attachBaseContext(BootstrapApplication.java:239)
at android.app.Application.attach(Application.java:211)
at android.app.Instrumentation.newApplication(Instrumentation.java:1020)
at android.app.Instrumentation.newApplication(Instrumentation.java:1004)
at android.app.LoadedApk.makeApplication(LoadedApk.java:666)
at android.app.ActivityThread.handleBindApplication(ActivityThread.java:6294)
at android.app.ActivityThread.access$1800(ActivityThread.java:222)
at android.app.ActivityThread$H.handleMessage(ActivityThread.java:1861)
at android.os.Handler.dispatchMessage(Handler.java:102)
at android.os.Looper.loop(Looper.java:158)
at android.app.ActivityThread.main(ActivityThread.java:7229)
at java.lang.reflect.Method.invoke(Native Method)
at com.android.internal.os.ZygoteInit$MethodAndArgsCaller.run(ZygoteInit.java:1230)
at com.android.internal.os.ZygoteInit.main(ZygoteInit.java:1120)
Caused by: java.lang.ClassNotFoundException: Didn't find class "android.support.multidex.MultiDexApplication" on path: DexPathList[[zip file "/data/app/com.yourapp.packagename-1/base.apk"],nativeLibraryDirectories=[/data/app/com.yourapp.packagename-1/lib/arm64, /vendor/lib64, /system/lib64]]
at dalvik.system.BaseDexClassLoader.findClass(BaseDexClassLoader.java:56)
at java.lang.ClassLoader.loadClass(ClassLoader.java:511)
at java.lang.ClassLoader.loadClass(ClassLoader.java:469)
at java.lang.Class.classForName(Native Method)
at java.lang.Class.forName(Class.java:324)
at java.lang.Class.forName(Class.java:285)
at com.android.tools.fd.runtime.BootstrapApplication.createRealApplication(BootstrapApplication.java:209)
at com.android.tools.fd.runtime.BootstrapApplication.attachBaseContext(BootstrapApplication.java:239)
at android.app.Application.attach(Application.java:211)
at android.app.Instrumentation.newApplication(Instrumentation.java:1020)
at android.app.Instrumentation.newApplication(Instrumentation.java:1004)
at android.app.LoadedApk.makeApplication(LoadedApk.java:666)
at android.app.ActivityThread.handleBindApplication(ActivityThread.java:6294)
at android.app.ActivityThread.access$1800(ActivityThread.java:222)
at android.app.ActivityThread$H.handleMessage(ActivityThread.java:1861)
at android.os.Handler.dispatchMessage(Handler.java:102)
at android.os.Looper.loop(Looper.java:158)
at android.app.ActivityThread.main(ActivityThread.java:7229)
at java.lang.reflect.Method.invoke(Native Method)
at com.android.internal.os.ZygoteInit$MethodAndArgsCaller.run(ZygoteInit.java:1230)
at com.android.internal.os.ZygoteInit.main(ZygoteInit.java:1120)
Suppressed: java.lang.ClassNotFoundException: android.support.multidex.MultiDexApplication
at java.lang.Class.classForName(Native Method)
at java.lang.BootClassLoader.findClass(ClassLoader.java:781)
at java.lang.BootClassLoader.loadClass(ClassLoader.java:841)
at java.lang.ClassLoader.loadClass(ClassLoader.java:504)
... 19 more
Caused by: java.lang.NoClassDefFoundError: Class not found using the boot class loader; no stack trace available
Clear and rebuild does not work. Uninstall and reinstall app does not work. Restart Android Studio still does not work.
After an hour struggling with this bug, I fix that by disable Instant Run and my app run fine again.
来源：https://stackoverflow.com/questions/39871338/unable-to-instantiate-application-caused-by-java-lang-classnotfoundexception-d