ABSTRACT. SET8, a member of the SET domain-containing methyltransferase, has been implicated in various biological processes. In this study, SET8 was immunostained in 100 samples of gastric cancer tissues and semi-quantified using the HSCORE method to determine the predictive value of SET8 expression levels for gastric cancer outcome. The relationship between SET8 expression and the 5-year survival rate of gastric cancer patients was assessed. High expression of SET8 was associated with a shorter survival time in gastric cancer patients, and the level of SET8 expression was found to be an independent predictor of gastric cancer outcome (relative risk = 1.939; 95% confidence interval = 1.025-3.668; P = 0.042). Analysis of SET8 levels may help in the identification of patient subgroups that are at high risk for poor disease outcomes.