〔Abstract〕 Objective To investigate the effect of chemotherapeutic drug resistance induced by CLDN18-ARHGAP26 fusion mutation gene in gastric cancer cells, and to investigate the sensitization effect of ginsenoside in the treatment of chemotherapeutic drug resistance caused by the expression of CLDN18-ARHGAP26 fusion mutation gene. Methods The side population(SP) cells and non-side population(NSP) cells of gastric cancer cell line BGC-823 were labeled with immunomagnetic bead antibody, and the lentiviral vector with overexpression of CLDN18-ARHGAP26 fusion mutation gene was selected for transfection with NSP cells.qPCR was used to detect the mRNA levels of CLDN18-ARHGAP26 fusion mutation and ATP Binding Cassette Subfamily G Member 2(ABCG2).The expression of EMT-related proteins E-Cadherin and Vimentin was detected by Western blot. The sensitivity of transfected cells to oxaliplatin was detected by CCK-8. The effect of ginsenoside on drug resistance of transfected cells was detected by CCK-8. The expression of E-Cadherin and Vimentin in transfected cells was detected by Western blot after ginsenoside treatment.Results qPCR detection showed that the expression ofCLDN18-ARHGAP26 fusion mutant gene in NSP cells transfected with overexpressedCLDN18-ARHGAP26 fusion mutant gene was significantly higher than that of the non-transfected group, and the expression of ABCG2 mRNA was significantly higher than that of the non-transfected group. Western bolt showed that the expression of E-Cadherin protein in NSP cells with over-expressedCLDN18-ARHGAP26 fusion mutation gene was lower than that in the non-transfected group, the expression of Vimentin protein was higher than that in the non-transfected group, and the sensitivity of transfected cells to oxaliplatin was lower than that in the non-transfected group. The survival rate of transfected cells treated with ginsenoside and oxaliplatin was significantly lower than that treated with oxaliplatin alone. The expression of E-Cadherin protein in the transfected cells treated with ginsenoside was higher than that in the untreated group, and the expression of Vimentin protein was lower than that in the untreated group.Conclusion Ginsenoside can reverse cell EMT transformation and oxaliplatin resistance induced byCLDN18-ARHGAP26 fusion mutated gene expression in gastric cancer tissues.