Objective To investigate the relationship between systemic lupus erythematosus (SLE) and hypothyroidism using bidirectional two-sample Mendelian randomization (MR) method. Methods The Genome-Wide Association Study data of SLE and hypothyroidism were obtained online. Independent single nucleotide polymorphisms closely related to SLE were screened as instrumental variable (IV), and outlier values were tested and eliminated by MR-PRESSO tool of R 4.3.1 software. The inverse variance weighted (IVW), MR-Egger, weighted mode (WM), weighted median (WME) and simple mode (SM) were used for MR analysis, and the values of odds ratio (OR) and 95% confidence interval (95%CI) were used to evaluate whether there was an association between SLE and hypothyroidism. The Cochran’s Q heterogeneity test was performed for the results of IVW and MR-Egger, the pleiotropy test was performed by Egger-intercept method, and the sensitivity analysis was performed by elimination test one by one. F value was calculated to evaluate whether there was a weak IV bias. Results MR analysis results showed that there was a positive causal relationship between SLE and hypothyroidism in the overall population, and the results calculated by IVW, MR-Egger, WM and WME were statistically significant, with OR (95%CI) being 1.004 (1.002-1.005), 1.004 (1.001-1.008), 1.004 (1.002-1.007), and 1.004 (1.002-1.006), respectively. The heterogeneity test results for IVW and MR-Egger were P＝0.086 and P＝0.098, respectively, indicating no heterogeneity; the Egger-intercept result was P＝0.295, indicating no pleiotropy; sensitivity analysis showed MR results were stable; and all F values were greater than 10, indicating no weak IV bias. Conclusion Compared with healthy people, the risk of hypothyroidism in patients with SLE is significantly higher.