A method and a system for pixel channel imbalance compensation for an image sensing circuit are provided. The system includes an image acquisition circuit having a lens, a color filter and an image sensor and a processing circuit. In the method performed by the processing circuit, a second frame image is retrieved from a motion image, and a first frame image that has undergone noise reduction can be retrieved from a memory. Motion detection is performed between the frames by comparing the first frame image and the second frame image. The motion detection is referred to as a reference for determining how to perform 3D noise reduction. A compensation value for channel imbalance between the adjacent channels can be estimated based on the image under noise reduction in a same buffer. While the pixel channel imbalance is compensated, the image is then restored by an interpolation method.