Based on the iterative least square and image registration technology,the iterative least square based algorithm (ILS) for nonuniformity correction of infrared focal plane arrays was presented,which greatly reduced the time and space complexity and made real-time realization of the image process possible.The ILS algorithm had the strength of accurate estimation of FPN,fast convergence rate and low computational complexity. The deduction of the algorithm has been presented and the effectiveness has been demonstrated by the simulation results.