【Objective】 To investigate the effects of emotions (subjective well-being, depressed effect, worry, and guilt) on cancer (colorectal cancer, hepatic cancer, thyroid cancer, lung cancer, and breast cancer). 【Methods】 Two-sample bi-directional Mendelian randomization (MR) method was adopted. All data were based on summary data from genome-wide association studies (GWAS). Inverse variance weighting (IVW) was used to generate the main results, and weighted median (WM) and MR-Egger methods were employed to calculate supplementary results. The outcome measure was odds ratio (OR), and sensitivity analysis was conducted. 【Results】 For depressed effect, a significant association with lung cancer (OR=1.005, 95% CI: 1.001-1.009, P=0.015) was found. For worry, a significant association with breast cancer (OR=1.199, 95% CI: 1.011-1.423, P=0.038) was observed. For guilt, a significant association with thyroid cancer (OR=2.083, 95% CI: 1.080-4.017, P=0.029) was identified. After removing all potentially pleiotropic SNPs detected by MR PRESSO, the association between worry and breast cancer showed no statistical difference (P=0.064), while the association between worry and colorectal cancer remained significant (OR=0.739, 95% CI: 0.571-0.956, P=0.021). No causal relationship was found between cancer and emotions. 【Conclusion】 There is a causal relationship between depression and increased lung cancer incidence, guilt and increased thyroid cancer incidence, as well as anxiety and decreased colorectal cancer incidence.