In order to increase the lifetime of the TDICCD imaging system in space and decrease the impact on the imaging quality for a long-time working in orbit, a system of real-time radiation correction in space is designed. It generates real-time correction parameters of multi-TDICCD channels and pixels in-channel by rotating the focus plane before the calculation of the real-time calibration images, and improves the adaptability and PRNU (pixel response non-uniformity) values of the TDICCD mosaic camera imaging system. FPGA is used to calculate and save the parameters, and an optimization design is implemented to improve the system stability and reliability. This method can calculate the real-time PRNU correction parameters of the TDICCD mosaic camera in-orbit, and the PRNU value of TDICCD mosaic camera in-channel reaches 2.01% after real-time calibration. This method is potentially used in real-time radiation calibration, and has got a better result.