The mortality cases caused by influenza virus are offen associated with the secondary bacterial infection, Streptococcus pneumoniae infection in particularly. The mechanisms underlying the interaction between the virus and the bacteria are unclear at present. The damage of normal protective epithelial layer and changes in airway function caused by influenza virus provides increased numbers of attachment sites and culture spaces for the bacteria. The effect of influenza on immune system is a further opportunity for subsequent bacterial infection. The synergistic effect between influenza virus and Streptococcus pneumoniae might not be unidirectional. The bacteria caused the secondary infection could enhance the pathogenicity of the virus. The bacterium-derived proteases could cleave hemagglutinin to its active components that are required for infectivity of the virus. The effect of the bacteria on the virus could enhance the lethality of the primary viral disease, which can explain why antibiotic therapy was less successful to treat the influenza patient with subsequent bacteria infection. Effective strategies to prevent and treat the severe diseases could be suggested based on the knowledge of interaction between virus and bacteria.