We demonstrated that CVB-D exhibits a kind of favorable anti-lung-cancer activity in vitro and in vivo and revealed a novel antitumor mechanism of CVB-D in lung cancer cells, namely that mitophagy-mediated mitochondrial dysfunction is a contributor to CVB-D-induced apoptotic death through the targeting of the p65/BNIP3/LC3 axis. The gene discussed is BNIP3; the disease is lung cancer.