Consistent with UVMR, the results of MVMR indicated that higher SNP-predicted cathepsin S expression remained robustly associated with a raised risk of colorectal cancer after adjusting for the other types of cathepsins (IVW: p = 0.0040, OR = 1.0725, 95%CI = 1.0233–1.1252), which were further supported by the MR-Egger method (p = 0.0030, OR = 1.0736, 95%CI = 1.0243–1.1252). Here, CTSS is linked to colorectal cancer.