Lung cancer is one of the most common human cancers and the leading cause of cancer-related death worldwide. The identification of lung cancer associated genes is essential for the diagnosis and treatment of this disease. Lung cancer metastasis-related protein 1 (LCMR1) is a novel gene cloned by differential display polymerase chain reaction in our laboratory. This study was designed to investigate the role of LCMR1 in the generation of apoptosis in lung cancer cells. RNA interference (RNAi) approach was used to knock down LCMR1 in lung cancer cells. The impacts of LCMR1 knockdown on the apoptosis of lung cancer cells were assessed using flow cytometry, quantitative real-time RT-PCR and western blotting. The results demonstrated that the inhibition of LCMR1 by RNAi enhanced apoptotic activity in lung cancer cells and this process required the involvement of p53. In addition, LCMR1 knockdown resulted in the upregulation of Bax and downregulation of Mcl-1. In conclusion, LCMR1 suppresses apoptosis in lung cancer cells and this effect is associated with multiple apoptosis-related proteins, including p53, Bax and Mcl-1. These results provide new insights into the potential role of LCMR1 in the regulation of lung cancer carcinogenesis.