Objective:To investigate the application value of double contrast-enhanced ultrasonography (DCEUS) combined with serum pepsinogen (PG) in the diagnosis of early gastric cancer(EGC).Methods:Eighty-two patients suspected of EGC from July 2020 to July 2022 in the People′s Hospital of Guangxi Zhuang Autonomous Region, and preoperative DCEUS examination and PG test were performed, and the patients were divided into benign lesion group(13 cases), early gastric cancer group(57 cases) and progressive gastric cancer group(12 cases) using postoperative pathology as the gold standard. Parameters for comparison included time to peak (TTP), peak intensity (PI), enhanced intensity (EI), serum pepsinogen Ⅰ (PGⅠ), serum pepsinogenⅡ (PGⅡ) and their ratio (PGⅠ/PGⅡ). The sensitivity, specificity, and accuracy of DCEUS and PG alone and in combination for the diagnosis of EGC were analyzed by plotting the ROC curve, and its diagnostic value was compared.Results:In the comparison of DCEUS parameters, PI and EI values were higher in the malignant group than in the benign lesion group and TTP was the opposite, with statistically significant differences (all P<0.05). In the comparison of PG detection, PGⅠ and PGⅠ/PGⅡ were lower in the malignant group than in the benign lesions, and lower in the progressive gastric cancer than in the EGC, while PGⅡ was the opposite, with statistically significant differences (all P<0.05). As shown by the ROC curve results, the sensitivity of DCEUS and PG alone and in combination for the diagnosis of EGC was 80.7%, 73.7% and 87.7%, respectively; the specificity was 76.0%, 72.0% and 80.0%, respectively; and the accuracy was 79.3%, 73.2% and 85.4%, respectively. The area under curve (AUC) of the two modalities alone and combined were 0.784 (95% CI=0.669-0.898), 0.728 (95% CI=0.606-0.850) and 0.839 (95% CI=0.734-0.943), respectively, and the combined diagnosis had a higher diagnostic value than the single diagnostic modality. Conclusions:The combined diagnostic modality of DCEUS and PG can further improve the diagnostic efficacy of EGC and reduce its underdiagnosis rate, which has good application value.