Gastric cancer (GC) is associated with poor patient prognosis, and so it crucial to investigate the molecular mechanisms underlying the progression of GC. The aim of the present study was to investigate the role of transmembrane-4 L6 family member 1 (TM4SF1) in the progression of GC. TM4SF1 small interfering RNA (siRNA) and TM4SF1-expressing plasmids were employed to regulate TM4SF1 expression. In vitro experiments were performed to determine the effect of TM4SF1 on the expression of apoptosis-associated molecules and determine the role of TM4SF1 in apoptosis, proliferation, migration and invasion using human GC cell lines MGC803 and MKN45. The data of the present study demonstrated that TM4SF1 may regulate the expression of apoptosis-associated molecules at the mRNA and protein levels. TM4SF1 silencing reduced B-cell lymphoma 2 (Bcl2) expression, whilst caspase-3 and Bcl2-associated X expression increased, and upregulating TM4SF1 reversed these changes in GC cells. Furthermore, TM4SF1 knockdown promoted apoptosis while inhibiting the proliferation, migration and invasion of GC cells. Rescue experiments demonstrated that TM4SF1 upregulation reversed the changes induced by transfection with TM4SF1 siRNA. In summary, TM4SF1 is an anti-apoptosis protein associated with the progression of GC. Additional in vivo experiments and clinical trials are required to confirm the possible use of TM4SF1 in tumor therapy.