Current methods of treatment for lung carcinoma are ineffective for the majority of patients. Conditionally replicating adenoviruses (CRAds) represent a potential novel treatment for a number of neoplastic diseases, including lung carcinoma. The present study aimed to investigate the synergistic mechanisms underlying the anti-angiogenesis gene, arresten, and the apoptosis-inducing gene, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), in order to evaluate their therapeutic potential in lung cancer. The two genes were expressed by CRAd, which was confirmed using reverse transcription-polymerase chain reaction and western blotting. In vitro analyses demonstrated that CRAd adenoviruses are capable of selectively inhibiting A549 lung cancer cell growth and replication but not in that of healthy cells. In vivo analyses demonstrated that the infection of A549 cell lines using CRAd armed with the two genes (CRAd-arresten-TRAIL) enhanced the tumor inhibition, compared with cells infected with CRAd-arresten, CRAd-TRAIL or CRAd, and with the control group. CRAd-arresten-TRAIL may therefore be useful in the treatment of lung cancer.