The defocusing of imaging plane for a space camera in severe space environments will effect the imaging quality. It is necessary to compensate the defocusing effectively for the space camera to improve the adaptabilities and to get a high quality image. A novel focusing system was designed for a multispectral camera with off-axis Three Mirror Anastigmat(TMA) system. Firstly, the focusing method was chosen, and the principle of focusing was described by analyzing the characteristics of the off-axis TMA system and the CCD focal plane. Then, the focusing system was introduced in detail, including the working condition of a focusing controller, the way to calculate the torque of a stepper motor,and the design parameters of focusing mechanism and the position sensor. Furthermore, the correlation between the focusing accuracy and focusing mechanism, sensor resolution was deduced. Finally, the relative curve of CCD position with an encoder was obtained in the focusing range by the proposed focusing system. Experimental result shows that the focusing accuracy in closed-loop control is ±3.11 μm (3σ). It can satisfy the system requirements of ±10 μm.