Our work highlights that (1) TRAIL effectively induces apoptosis in cisplatin-resistant GC cells; (2) the JWA/MARCH8/DR4 axis controls the effect of TRAIL on cisplatin-resistant human GC cells; and (3) JWA is a potential predictive marker of TRAIL sensitivity in GC, thus indicating its significance in clinical personalized therapeutics. This evidence concerns the gene TNFRSF10A and gastric cancer.