PurposeSerum uric acid (SUA) has antioxidant capacities and therefore may protect against the development of cancer. Few epidemiological studies have tested this hypothesis, and findings were inconsistent.MethodsWe studied the association between SUA levels and mortality due to any type of cancer, and three common types of cancer among males (lung, colorectal, and prostate cancer) in the general population-based Vlagtwedde–Vlaardingen cohort with 38 years of follow-up and 8 surveys (total number of males = 4,350). Of 1,823 males with data available on SUA, 254 (13.9 %) died due to any cancer (lung n = 75 (4.1 %), colorectal n = 27 (1.5 %), and prostate cancer n = 23 (1.3 %), assessed on 31 December 2008). SUA, cholesterol, and triglyceride were measured in males during the surveys in 1970, 1972, and 1973. We analyzed the association between cancer mortality risk and SUA level both as continuous variable and as tertiles: lowest <5 mg/dl (reference), middle 5–5.8 mg/dl, and highest >5.8 mg/dl, using multivariate Cox regression with adjustment for age, smoking (pack years), and body mass index.ResultsHigher levels of SUA were associated with a lower risk of mortality from any cancer [HR (95 % CI) = 0.85 (0.73–0.97)]. SUA levels in the highest tertile (>5.8 mg/dl) were associated with a lower risk of mortality from any cancer [0.68 (0.48–0.97)]. Additional adjustment for serum total cholesterol and triglyceride levels did not change the results.ConclusionsOur study indicates that elevated SUA levels may protect against cancer mortality.