Gastric cancer (GC) is one of the most common malignant tumors and the Kazakh population in Xinjiang has been reported to be one of the highest incidence of GC in the world. Serum pepsinogen (PG) test provides a valuable method for detecting GC, but little study about the role of PG in Kazakh GC. Therefore, we aimed to investigate the role of PG in Kazakh GC and to elucidate the usefulness of the serum PG test method. The serum PG concentration were measured using the flow fluorescence assay and ELISA methods in patients with superficial gastritis, atrophic gastritis and GC. The most suitable cut off point was a PG I concentration ≤64 ng/ml and PG I/II ratio (PGR) ≤4.5. Using this cut off point, the sensitivity and specificity of pepsinogen screening for Kazakh GC were 80.5% and 89.8%, respectively. The area under the curve (AUC) of the PGR for GC diagnosis was 0.949, which was significantly higher than that of combined tumor markers. Moreover, PGR in Kazakh early GC was statistically significantly lower than in SG and AG. These findings suggest that serum PG test can serve as a noninvasive biomarker for the diagnosis of Kazakh GC.