Hypersensitivity to radiation exposure has been suggested to be a risk factor for the development of several malignancies, but not including gastric cancer. In this case-control study, radiation sensitivity as measured by chromatid breaks per cell (b/c) was examined in cultured peripheral blood lymphocytes (PBLs) from 517 patients with gastric cancer and 525 healthy controls. Our results showed that b/c values were significantly higher in cases than in controls (Mean [SD], 0.47 [0.20] vs. 0.34 [0.17]; P<0.001). Using the 50(th) percentile value for controls (0.34 b/c) as the cutoff point, unconditional logistic regression analysis revealed that γ-radiation-sensitive individuals were at significantly higher risk for gastric cancer (adjusted odds ratio [OR] 2.01, 95% confidence interval [CI] 1.49-3.13). Quartile stratification analysis indicated a dose-response relationship between γ-radiation sensitivity and gastric cancer risk (P for trend <0.001). When using the subjects in first quartile of b/c values as reference, the adjusted ORs and corresponding CIs for the subjects in second, third, and fourth quartiles were 1.48 (0.91-2.17), 2.42 (1.76-3.64), and 3.40 (2.11-5.29), respectively. The γ-radiation sensitivity was related to age and smoking status. In addition, a clear joint effect on cancer risk was found between γ-Radiation sensitivity and smoking status. The risk for ever smokers with high sensitivity was higher than those for never smokers with high sensitivity and ever smokers with low sensitivity (OR [CI], 4.67 [2.31-6.07] vs. 2.14 [1.40-3.06] vs. 2.42 [1.57-3.95], respectively). No significant interaction was found between both factors (P for interaction= 0.42). We conclude that chromatid radiosensitivity is associated with gastric cancer susceptibility in a Chinese population.