The aim of the study was to estimate the value of detecting pepsinogen (PG) I, PGII, and gastrin-17 (G-17) levels in serum for chronic atrophic gastritis (CAG) screening and to determine the clinical applicability of combined measurement of serum G-17, pepsinogens (PGI, PGII) and PGI/PGII ratio (PGR) as a screening test for CAG. The PGI, PGII, and G-17 levels were detected by ELISA in 68 patients with CAG and 86 healthy volunteers who underwent gastroscopy for gastroduodenal diseases at Taizhou Municipal Hospital between January 2016 and December 2016. Concentrations of all measured serum markers were lower in patients with CAG in comparison to healthy volunteers and achieved statistical significance (P<0.01) in PGI (93.25 vs 126.98) and PGR (12.67 vs 17.09). Receiver operating characteristic (ROC) curve analysis revealed the optimal cut-off values for PGI, PGII, PGR, and G-17 at 98.10 μg/l, 6.92 ng/l, 15.77 and 1.94 pmol/l, with sensitivities of 72.10%, 58.10%, 61.60%, and 59.30% and specificities of 61.8%, 51.50%, 77.90%, and 55.90%, respectively. The areas under the curve (AUCs) of PGI, PGR, and G-17 were 0.728, 0.726, and 0.556, respectively. The increase of AUC was observed only in PGR and G-17 combination (0.741) with increased sensitivity (69.10% vs 61.60%) of screening for CAG, whereas the specificity was reduced (72.10% vs 77.90%) in comparison to PGR alone. Combination of serum indicators can raise the diagnosis accuracy of CAG in some respects. However, further research including a larger sample size is necessary in order to accurately determine the sensitivity and specificity of combined detection of serum indicators.