Purpose M30 and M65 are different circulating fragments of cytokeratin 18. They release during apoptotic cell death, so it is believed that they reflect cell death of epithelial tumors. The aim of this study was to determine the prognostic value of plasma M30 and M65 levels in predicting of survival for patients with advanced gastric cancer compare with healthy controls. Methods Thirty-four patients with advanced gastric cancer and thirty-two healthy controls were included. Plasma M30 and M65 values were measured by quantitative ELISA method. Results The median age of patients and control groups was 60 and 56 years, respectively. No difference was detected between patient and control groups with respect to plasma median M30 values (390.4 vs. 270.7 U/l, respectively, P  = 0.10). The median plasma M65 values of patients were significantly higher than those of control group (1232.1 vs. 580.1 U/l, P  < 0.001). The best cut-off values for plasma M30 and M65 for predicting progression-free survival (PFS) were 277.7 and 1434.9 U/l in ROC analysis. The patients whose plasma M30 values were higher than 277.7 U/l had worse PFS than patients with plasma M30 value <277.7 U/l (8.9 vs. 11.2, respectively, P  = 0.01). The median PFS of patients whose M65 levels lower than or equal to 1434.9 U/l was better than that of patients whose M65 levels were >1434.9 U/l (12.4 vs. 10.4, respectively, P  = 0.04). But plasma M30 and M65 level in patient group were not found to be an important prognostic factor for PFS in the multivariate analysis. Conclusions These results showed that plasma M65 values were significantly elevated in patients with advanced gastric cancer compared to healthy people. Moreover, both increased plasma M30 and M65 levels can predict PFS in patients with gastric cancer.