We designed to understand the effects of the T1151A gene polymorphism in the hMLH1 gene on the pathogenesis of familial gastric cancer. Peripheral blood DNA from 113 patients with familial gastric cancer or suspected familial gastric cancer that were newly identified in the same year, along with 180 healthy subjects, was subjected to polymerase chain reaction-denaturing high-performance liquid chromatography (PCR-DHPLC) and DNA sequencing of exon 12 in the hMLH1 gene. Our results as following, the T1151A detection rate was remarkably higher in patients with familial gastric cancer or suspected familial gastric cancer compared to normal control patients (P < 0.05). Stratified analysis showed that there was a significant difference in the detection rate between the control group and elderly patients whose age of onset was greater than 50 years old (P < 0.05). The detection rate of patients from high-risk families were relatively high (P < 0.05). An especially significant distribution was observed in patients who had suffered precancerous diseases related to gastric cancer (P < 0.01). In conclusion, familial gastric carcinoma families in China carrying the T1151A polymorphism may have a higher risk of suffering from gastric cancer. This gene polymorphism can be used as a candidate screening index for high-risk populations.