diff --git a/src/posix/platform/hdlc_interface.cpp b/src/posix/platform/hdlc_interface.cpp
index 64183dd1d..96ae4cfe6 100644
--- a/src/posix/platform/hdlc_interface.cpp
+++ b/src/posix/platform/hdlc_interface.cpp
@@ -250,13 +250,12 @@ exit:
 
 otError HdlcInterface::WaitForFrame(const struct timeval &aTimeout)
 {
-    otError        error   = OT_ERROR_NONE;
-    struct timeval timeout = aTimeout;
-
+    otError error = OT_ERROR_NONE;
 #if OPENTHREAD_POSIX_VIRTUAL_TIME
     struct Event event;
+    uint64_t     delay = static_cast<uint64_t>(aTimeout.tv_sec) * US_PER_S + static_cast<uint64_t>(aTimeout.tv_usec);
 
-    virtualTimeSendSleepEvent(&timeout);
+    virtualTimeSendSleepEvent(&aTimeout);
     virtualTimeReceiveEvent(&event);
 
     switch (event.mEvent)
@@ -266,7 +265,7 @@ otError HdlcInterface::WaitForFrame(const struct timeval &aTimeout)
         break;
 
     case OT_SIM_EVENT_ALARM_FIRED:
-        ExitNow(error = OT_ERROR_RESPONSE_TIMEOUT);
+        VerifyOrExit(event.mDelay <= delay, error = OT_ERROR_RESPONSE_TIMEOUT);
         break;
 
     default:
@@ -274,6 +273,8 @@ otError HdlcInterface::WaitForFrame(const struct timeval &aTimeout)
         break;
     }
 #else  // OPENTHREAD_POSIX_VIRTUAL_TIME
+    struct timeval timeout = aTimeout;
+
     fd_set read_fds;
     fd_set error_fds;
     int rval;
diff --git a/src/posix/platform/include/openthread/openthread-system.h b/src/posix/platform/include/openthread/openthread-system.h
index e582cbfe3..476940563 100644
--- a/src/posix/platform/include/openthread/openthread-system.h
+++ b/src/posix/platform/include/openthread/openthread-system.h
@@ -82,6 +82,11 @@ enum
      * System call or library function error.
      */
     OT_EXIT_ERROR_ERRNO = 5,
+
+    /**
+     * No response from radio spinel.
+     */
+    OT_EXIT_RADIO_SPINEL_NO_RESPONSE = 6,
 };
 
 /**
diff --git a/src/posix/platform/misc.cpp b/src/posix/platform/misc.cpp
index e26e96eec..a5cd1da65 100644
--- a/src/posix/platform/misc.cpp
+++ b/src/posix/platform/misc.cpp
@@ -133,6 +133,10 @@ const char *otExitCodeToString(uint8_t aExitCode)
         retval = "RadioSpinelReset";
         break;
 
+    case OT_EXIT_RADIO_SPINEL_NO_RESPONSE:
+        retval = "RadioSpinelNoResponse";
+        break;
+
     case OT_EXIT_ERROR_ERRNO:
         retval = strerror(errno);
         break;
diff --git a/src/posix/platform/radio_spinel.cpp b/src/posix/platform/radio_spinel.cpp
index c49d26b38..5673f6c68 100644
--- a/src/posix/platform/radio_spinel.cpp
+++ b/src/posix/platform/radio_spinel.cpp
@@ -1237,36 +1237,26 @@ otError RadioSpinel::Remove(spinel_prop_key_t aKey, const char *aFormat, ...)
 
 otError RadioSpinel::WaitResponse(void)
 {
-    uint64_t       now     = platformGetTime();
-    uint64_t       end     = now + kMaxWaitTime * US_PER_MS;
-    struct timeval timeout = {kMaxWaitTime / 1000, (kMaxWaitTime % 1000) * 1000};
+    uint64_t end = platformGetTime() + kMaxWaitTime * US_PER_MS;
+
+    otLogInfoPlat("Wait response: tid=%u key=%u", mWaitingTid, mWaitingKey);
 
     do
     {
-        if (mSpinelInterface.WaitForFrame(timeout) == OT_ERROR_RESPONSE_TIMEOUT)
-        {
-            FreeTid(mWaitingTid);
-            mWaitingTid = 0;
-            ExitNow(mError = OT_ERROR_RESPONSE_TIMEOUT);
-        }
+        uint64_t       now;
+        uint64_t       remain;
+        struct timeval timeout;
 
         now = platformGetTime();
+        VerifyOrDie(end > now, OT_EXIT_RADIO_SPINEL_NO_RESPONSE);
+        remain = end - now;
 
-        if (end > now)
-        {
-            uint64_t remain = end - now;
+        timeout.tv_sec  = static_cast<time_t>(remain / US_PER_S);
+        timeout.tv_usec = static_cast<suseconds_t>(remain % US_PER_S);
 
-            timeout.tv_sec  = static_cast<time_t>(remain / US_PER_S);
-            timeout.tv_usec = static_cast<suseconds_t>(remain % US_PER_S);
-        }
-        else
-        {
-            mWaitingTid = 0;
-            mError      = OT_ERROR_RESPONSE_TIMEOUT;
-        }
+        VerifyOrDie(mSpinelInterface.WaitForFrame(timeout) == OT_ERROR_NONE, OT_EXIT_RADIO_SPINEL_NO_RESPONSE);
     } while (mWaitingTid || !mIsReady);
 
-exit:
     LogIfFail("Error waiting response", mError);
     // This indicates end of waiting repsonse.
     mWaitingKey = SPINEL_PROP_LAST_STATUS;