〔Abstract〕 Objective To explore the relationship between pepsinogen, gastrin-17 and the progression of gastroesophageal reflux disease (GERD). Methods A total of 150 GERD patients admitted to Huizhou Hospital of Traditional Chinese Medicine from February 2019 to February 2021 were selected, and they were divided into non-erosive esophagitis (NERD) group, erosive esophagitis (EE) group and Barrett in the esophagus (BE) group according to the examination results, with 50 cases in each group, the levels of serum pepsinogen Ⅰ, Ⅱ and gastrin-17 were detected by quantum dot fluorescence immunoassay and the correlation between the levels and the severity of GERD was analyzed. Receiver operating characteristic curve (ROC) was used to analyze the diagnostic efficiency of serum pepsinogen Ⅰ, Ⅱ and gastrin-17 for GERD. Results Serum levels of pepsinogen I and gastrin-17 in three groups: BE group > EE group > NERD group; pepsinogen II level: NERD group > EE group > BE group, the differences were statistically significant (P < 0.05). Pepsinogen I, gastrin-17 were positively correlated with the severity of GERD, and the differences were statistically significant (P < 0.05). Pepsinogen II was negatively correlated with the severity of GERD, and the difference was statistically significant (P < 0.05). The receiver operating characteristic curve (ROC) showed that the cut-off value of pepsinogen I was > 136.98 μg·L-1, the area under the curve for diagnosing GERD was 0.788, the sensitivity was 84.00 %, and the specificity was 74.00 %; The cut-off value of pepsinogen II was ≤ 7.99 μg·L-1, the area under the curve for the diagnosis of GERD was 0.698, the sensitivity was 70.00 %, and the specificity was 78.00 %; The cut-off value of gastrin-17 was > 2.55 pmol·L-1, the area under the curve for the diagnosis of GERD was 0.848, and the sensitivity was 0.848, the specificity was 85.00% and the specificity was 88.00%. Conclusion With the progress of GERD, the levels of pepsinogen I and gastrin-17 increase and pepsinogen II decrease. The above indexes have high sensitivity and specificity in the diagnosis of GERD, which is expected to become a serological index for screening GERD due to their convenience and cheapness.