Objective:To investigate the correlation between telomere dysfunction of human gastric mucosa and chronic atrophic gastritis (CAG).Methods:From February 12, 2019 to July 10, 2020, at Endoscopy Center, Guang′anmen Hospital, China Academy of Chinese Sciences, 30 patients received endoscopy and pathological diagnosed with CAG (CAG group) were collected, and 30 patients with chronic non-atrophic gastritis (CNAG) were collected at the same time (CNAG group). The relative telomere length was detected by real time fluorescent quantitative polymerase chain reaction. The expression of telomere repeat binding factor (TRF) 1, TRF2 and protection of telomere (POT) 1 at protein level were detected by immunohistochemical staining and semi-quantitative analysis. Spearman analysis was used to analyze the correlation between the relative telomere length of gastric mucosa and the protein expression levels of TRF1, TRF2 and POT1. Mann-Whitney U test and independent sample t test were used for statistical analysis. Results:The relative telomere length of the gastric mucosa in the CAG group was shorter than that in the CNAG group (0.67 (0.51 to 1.17) vs. 1.06(0.69 to 1.37)), and the difference was statistically significant ( U=297.00, P=0.024). The protein expression levels of TRF1, TRF2, and POT1 in the CAG group were all higher than those in the CNAG group, respectively (4.26±2.49 vs. 1.86±1.34, 10.12±2.76 vs. 8.78±2.81, 4.22±2.48 vs. 2.53±1.62), and the differences were statistically significant ( t=8.05, 3.23, 5.39; P<0.001, =0.001, and <0.001). In the CAG group, the protein expression levels of TRF2 and POT1 in gastric mucosa were negatively correlated with the relative telomere length ( r=-0.477 and -0.417, P=0.008 and 0.022). Conclusions:The telomere dysfunction is related to the pathogenesis of CAG. The change of telomere binding protein expression level is involved in the shortening of telomere and pathological process of CAG patients.