AKAP12α plays an important role in tumour growth suppression by inducing apoptosis. This study investigated whether the promoter methylation of AKAP12α is associated with lung cancer. AKAP12α was down-regulated in lung cancer cells and the reduced protein expression was restored by DNA methyl-transferase inhibitor. AKAP12α promoter was more frequently methylated in tumours than in normal tissues. Furthermore, AKAP12α methylation was found more frequently in the cells of non-relapse patients after surgery than in those of early relapse patients. In conclusion, this study demonstrated that AKAP12α expression is regulated by DNA methylation and that AKAP12α promoter methylation is associated with lung cancer prognosis.