Protein phosphatases play critical roles in regulating cell division, cell apoptosis, and cell cycle in eukaryotic cells, participating in numerous signal transduction processes and exerting a large amount of significant biological functions. A variety of protein phosphatases are identified to maintian the phosphorylation level of key proteins with a moderate level in the antiviral innate immune response to virus infection. In this paper, we reviewed the roles of serine/threonine protein phosphatases, tyrosine protein phosphatases, and lipid phosphatases in regulating antiviral innate immune responses.