The prognostic role of Human leukocyte antigen class I (HLA- I) in gastrointestinal cancers has been remained controversial. We performed a meta-analysis to determine the role of classical HLA-I in predicting survival of patients. In addition, the relationship between HLA- I and some clinicopathological factors was evaluated. Published studies investigated HLA-I expression effect on gastrointestinal cancers were evaluated to determine association between HLA- I and overall survival (OS) and recurrence-free survival (RFS) in patients. The used effect sizes were hazard ratio (HR) and Odds ratio (OR) with 95% confidence interval (CI). A total of ten studies included 1307 patients were analyzed. The pooled results revealed that HLA- I overexpression was positively related to OS (HR: 0.72; 95% CI: 0.53-0.96) and demonstrated little association for RFS (HR: 0.70; 95% CI: 0.46-1.08). HLA-I overexpression is negative associated with poorer differentiation of tumor (OR: 0.53; 95% CI (0.43-0.81) and also higher stages of cancer (OR: 0.29; 95% CI (0.13-0.64). HLA- I overexpression was related to a better prognosis on OS and probably had little impact on RFS.