Irisin is a recently discovered myokine/adipokine and lower levels of irisin were proved to be associated with adverse outcomes of cardiovascular and cerebrovascular diseases (CCVD) in general population. A significant decrease of irisin concentrations were also detected in patients with chronic kidney disease (CKD). In the present study, we investigated whether the serum irisin levels were associated with cardiovascular and cerebrovascular mortality in hemodialysis (HD) patients. This retrospective cohort study enrolled 152 HD patients. Kaplan-Meier analysis was used to estimate the cumulative mortality of CCVD. The differences between the survival curves were compared by log-rank test. A multivariable Cox regression analysis was employed to identify the predictors of CCVD related deaths. Among 152 HD patients, 55 patients died and 18 of them died of CCVD, 97 HD patients survived. Compared with the survival group, patients died of CCVD had significantly lower serum irisin levels [23.6 (2.2, 319.4) vs. 45.7 (2.1, 367.8) ng/mL, P<0.05]. The Kaplan-Meier survival curves showed that patients with lower levels of irisin had higher CCVD mortality. The Cox regression analysis indicated lower irisin level as an independent risk factor for CCVD mortality in HD patients but not for all-cause mortality. Our results provided an association between lower irisin level and CCVD mortality in HD patients. Lower levels of irisin increased the mortality of CCVD in HD patients.