We have been investigating gene expression profiles in non-small cell lung cancers (NSCLCs) to identify molecules involved in pulmonary carcinogenesis and select which genes or gene products might be useful as diagnostic markers or targets for new molecular therapies. Here we report evidence that the cytochrome c oxidase (CCO) assembly protein COX17 is a potential molecular target for treatment of lung cancers. By semiquantitative reverse transcription-PCR, we documented increased expression of COX17 in all of 8 primary NSCLCs and in 11 of 15 NSCLC cell lines examined, by comparison with normal lung tissue. Treatment of NSCLC cells with antisense S-oligonucleotides or vector-based small interfering RNAs of COX17 suppressed expression of COX17 and also the activity of CCO, and suppressed growth of the cancer cells. Because our data imply that up-regulation of COX17 function and increased CCO activity are frequent features of lung carcinogenesis, we suggest that selective suppression of components of the CCO complex might hold promise for development of a new strategy for treating lung cancers.