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Background: Several studies have reported that low serum uric acid (SUA) levels are related to increased risk of mortality in maintenance hemodialysis (MHD) patients. However, the possible detrimental effects of high SUA on the mortality risk have not been well examined. Moreover, the possible effect modifiers for the SUA-mortality association have not been fully investigated. To address the aforementioned gap, we aimed to explore the nonlinear relationship between SUA levels and all-cause and cardiovascular disease (CVD) mortality risk, and to examine any possible effect modifiers in MHD patients. Methods: We conducted a multicenter, prospective cohort study among 1,018 MHD patients from 8 hemodialysis centers. The primary outcome was all-cause mortality, and the secondary outcomes were CVD mortality and non-CVD mortality. Results: The mean value for SUA in the total population was 8.5 ± 1.9 mg/dL. The lowest and highest quintiles of SUA were 10.1 mg/dL, respectively. Over a median follow-up of 45.6 months, 343 deaths were recorded, of which 202 (58.9%) were due to CVD. When SUA was assessed as quintiles, a significantly higher risk of all-cause mortality was found in patients in quintile 1 (p for interaction = 0.018). Similar trends were found for CVD mortality and non-CVD mortality. Conclusion: There was a U-shaped relationship between SUA levels and the risk of all-cause mortality, CVD mortality, and non-CVD mortality in MHD patients.