In the present study, the effects of the co-transfer of the tumor growth inhibitor 4 gene (ING4) together with the Oncostatin M (OSM) were investigated on tumor regression and subsequent tumor recurrence. We constructed a recombinant adenovirus carrying ING4 and OSM, which could induce high-level expression of these three genes in NPC CNE-1 cells. Ad-ING4, Ad-OSM and Ad-ING4-OSM infection all inhibited the growth of CNE-1 cells in vitro, while the Ad-ING4-OSM exerted the strongest inhibitory effect. In CNE-1 xenograft tumor models mice, an intratumoral injection of Ad-ING4, Ad-OSM and Ad-ING4-OSM resulted in a reduced tumor burden, compared to normal saline controls. Therefore, we suggested that the introduction of adenovirus-mediated ING4 and OSM genes could synergistically decrease the recurrence or metastases and develop a control of NPC tumors, which advocate a promising therapeutic future in NPC treatment.