An encoding method of screen frame and its application of electronic devices, which rapidly detect motion regions and motionless regions from lossless screen frames captured by software, and then encode the motion regions with lower image quality while encode motionless regions with higher quality to display higher quality images and smooth video at a receiving end in real-time. Furthermore, the above-mentioned encoding method is optimized for lossless screen frames which does not need complicated operations of video encoder of prior art, such as motion estimation, motion compensation, etc., so that the method can be implemented with minor system resources and lower latency delay.