An effective algorithm is designed for incorporating in a 3D stacked CMOS image sensor for image denoising in ultra-low light conditions. The algorithm originates from sparsity-prior of image and non-locally clustered sparse representation. The simulation results of the CIS image signal processing (ISP) demonstrate high-performance at intense noise level of ultra-low light images, which reveal a great potential of the CIS design in various applications such as night shot, security monitoring, machine-state inspection, medical imaging, biophysics detection, etc.