CZTSSe is a promising clean photovoltaic material; however, in fact, the power conversion efficiency (PCE) of CZTSSe solar cells is still far below the maximum theoretical efficiency, and one of the important reasons is the crystallographic factors that limit the performance of CZTSSe. In this chapter, SCAPS-1D is used to simulate the performance of CZTSSe cells with MoS2 as the HTL layer, focusing on the simulation of the thickness ratio, defect density of MoS2, WS2/CZTSSe, and CZTSSe/MoS2 interface defect density. The optimal thicknesses of the CZTSSe and MoS2 are determined to be 400 and 1600 nm. It is found that the interface defects of the buffer layer and the absorption layer have a significant impact on the performance of the battery, and the expected reasons are given. Finally, the optimized PCE can reach 22.31%. This work may be helpful for the application of MoS2 in CZTSSe solar thin-film cells, and make a little contribution to the continuous development of CZTSSe solar cell research.