Background: Hepatitis E virus (HEV) infection is an important emerging health issue in patients on hemodialysis (HD). To date, numerous studies have reported controversial findings regarding the seroprevalence of HEV among this high-risk group around the world. The aim of the present study was to estimate the overall seroprevalence of HEV in HD patients. Methods: A systematic literature search was carried out using PubMed, Web of Science, Scopus, Embase, and Google scholar from inception to January 10, 2020 with standard keywords. Pooled seroprevalence estimates with 95% confidence intervals (CI) were calculated using a random intercept logistic regression model. Results: A total of 56 studies met the inclusion criteria compromising 9483 HD patients. The pooled seroprevalence of HEV was estimated 9.31% (95%CI: 6.83%-12.57%). The seroprevalence of HEV was increased from 6.6% between the years of 1994 and 2000 to 11.13% from the year of 2016 to 2020. Blood transfusion was associated with a nearly twofold increase in the rate of HEV seropositivity (OR=1.99; 95%CI: 1.50-2.63, P value < 0.0001, I 2 =6.5%). Conclusions: Our results indicated an increased exposure of HD patients with HEV infection over the last decade. We concluded that blood transfusion, age and duration of HD are considerable risk factors for acquiring HEV infection among HD patients.