Objectives Influenza viruses are able to cause annual epidemics and pandemics due to their mutation rates and reassortment capabilities leading to antigenic drifts and antigenic shifts. To understand host response to influenza A and B viruses on A549, MDCK II cell lines at low and high MOIs, the effects of the viral infection were investigated. To identify virus host interplay, expression of MxA and caspases 3, caspases 7 and caspases 9, BAD, TNF α and IkBα genes were measured in the cells supernatants. Methods Cell viability and apoptosis were evaluated by LDH measurement, DNA fragmentation, and florescent staining. The resulting data points to all viruses of studied strains induced extrinsic and intrinsic apoptosis, H1N1 and H3N2 respectively prefer initially enhances the intrinsic pathway, as determined by caspase 9 activity and INFB prefer intrinsic pathway according to caspase 8 activity in A549 cell line but also can choose extrinsic pathway as determined by caspase 9 activity MDCKII cells. Results The result suggests a role for IFN response in the replication of influenza A and B virus that may provide some degree of host resistance in the early stages of infection. Our study also showed that the considerable MxA expression was found in influenza A and B virus, infected A549 and MDCK II cells at low dose of the virus. Conclusions The expression levels of survival downstream targets of IκB protein level, including pro-apoptotic BAD levels were studied throughout the infection periods cells to influenza A and B induced apoptosis signaling via intrinsic and extrinsic pathways in parallel, and the induction was associated with viral infection in a dose dependent manner.