Endoplasmic reticulum membrane protein complex subunit 6 (EMC6), also known as transmembrane protein 93 (transmembrane protein 93, TMEM93), is an autophagy-related protein. EMC6 overexpression inhibits cancer cell growth and induces apoptosis, but the interaction partners of EMC6 and its cellular responsibilities remain incompletely understood. In this study, we report that adenovirus-mediated ectopic overexpression of EMC6 (Ad5-EMC6) in BGC823 and SGC7901 gastric cancer cells decreases the activity of ERK1/2, down-regulates the levels of BCL-2 protein and phosphorylated BCL-2, increases the expression of tBID and BAX, and decreases mitochondrial membrane potential and subsequently leading to cell apoptosis. In a xenograft tumor model, we found that Ad5-EMC6 impairs the tumorigenesis of SGC7901 gastric cancer cells in nude mice. Additionally, Ad5-EMC6 enhances the sensitivity of gastric cancer cells to the chemotherapeutic drug etoposide. Collectively, these results demonstrate that EMC6-induced apoptosis of gastric cancer cells occurs at least partially through the mitochondrial-mediated apoptosis pathway. Our study suggests a rational basis for the potential clinical application of Ad5-EMC6 in gastric cancer. (C) 2019 Elsevier Inc. All rights reserved.