Highly expressing GHET1 promoted the development of MDR which was related to the Bax, Bcl-2, MDR1 and MRP1 genes expression in gastric cancer cells. In the BGC823 and SGC7901 cell, overexpression of GHET1 downregulated Bax expression and upregulated Bcl-2, MDRA and MRP1 expression, which resulted in increasing cisplatin resistance and inhibiting cell apoptosis. In the BGC823/DPP and SGC7901/DDP cell, knockdown of GHET1 leaded to increase cisplatin sensitivity and promote cell apoptosis. In the present study, we examined the GHET1 expression level in gastric carcinoma tissues of cisplatin sensitive patients and drug-resistant patients, as well as the MDR gastric cancer cell lines and their chemo-sensitive parental line. We also identified the function of GHET1 in cisplatin resistant strains (BGC823/DPP and SGC7901/ DDP cells) and their parental line (BGC823 and SGC7901 cells) using gain-of-function and loss-of-function approaches in vitro.