The relationship between systemic lupus erythematosus (SLE) and hepatitis B virus (HBV) infection is still unclear. We conducted a two-sample Mendelian randomization (MR) analysis using summary statistics from genome-wide association studies for SLE and HBV infection in individuals of East Asian ancestry. The inverse-variance weighted (IVW) method, weighted median (WM) method, and MR-Egger method were used to estimate the causal effect of SLE on HBV infection. Additionally, we performed a multivariable MR analysis adjusting for the effects of body mass index and rheumatoid arthritis. This MR study included a total of 225 106 individuals of East Asian ancestry, comprising 5616 cases and 219 490 controls. The IVW method (OR: 0.79, p = 3.34E-08) and the WM method (OR: 0.79, p = 9.09E-06) revealed a causal relationship between genetically predicted SLE and a low risk of HBV infection. The multivariable MR analysis still suggested a low risk of HBV infection associated with SLE (OR: 0.83, p = 2.89E-06). Our MR analysis supports a causal relationship between SLE and a low risk of HBV infection in individuals of East Asian ancestry.