Multi-parameter joint optimization is a trend in lithography resolution enhancement techniques. A multi-parameter joint optimization method for lithography based on the 3D topography difference of photoresist was proposed herein. By using the error of photoresist pattern at multiple depth positions as an objective function, the light source, the mask, the wavefront of the projection objective lens, the defocusing amount, and the exposure dose were jointly optimized, which improved the quality of the 3D topography of photoresist pattern. To obtain higher optimization efficiency, the adaptive differential evolution algorithm was adopted to optimize the light source and the mask, and different optimization methods were employed based on the characteristics of other parameters. The simulation results of dense lines, complex mask patterns with cross gate structure, and typical patterns in the static random access memory show that the maximum possible focal depth is 237 nm, 115 nm, and 144.8 nm, and the maximum exposure latitude is 18.5%, 12.4%, and 16.4%, respectively. Compared with the joint optimization technology of light source mask projection objective lens based on aerial image, the proposed method provides much larger process window.