Apoptosis is a tightly regulated process important for the host's defense mechanism for eliminating invading pathogens. Some viruses have evolved various strategies to prevent or delay the host cell apoptosis in order to archive viral replication inside host. For instance, several virus’s express protein homologous in structure and function to mammalian pro-survival Bcl-2 proteins. A TNP16L expressed by tana-pox virus is crucial for survival of infected cells. Although, there was no any closest sequence homology proteins other than its immediate ortholog in other pox viruses such as deer-pox virus DPV022. Here we report that the crystal structure of TNP16L reveals a Bcl-2-like fold with an unusual N-terminal extension. Protein itself forms a domain-swapped dimer in which the alpha1 helix is the exchanged domain. Binding studied have been showed that it follows typical BH3 binding profile with wide range of affinities towards BH3 peptides where it didn’t bind to Bok and Noxa. Site-directed mutagenesis revealed a site in TNP16L that was critical for the interaction with BH3 peptide and blocking DNA damage-induced cell death, highlighting a targetable vulnerability in TNP16L that could be exploited therapeutically. Our findings provide a detailed mechanistic understanding for the potent anti-apoptotic activity of TNP16L during tana-pox virus infection.