ATP2A2 is a member of ATP2As family; it encodes SERCA2b,a sarco(endo)plasmic reticulum calcium transport ATPases (SERCAs). As the main function of SERCA2b is to transport calcium from the cytosol to the sarco(endo)plasmic reticulum, it plays a vital role in numerous calcium-related signaling pathways involving control of tumor growth, differentiation, angiogenesis, metastasis and apoptosis. Recent studies have identified the accurate change of ATP2A2 expression in some tumors, which makes the first step in investigating how ATP2A2 participates in tumorigenesis and whether it can be taken as a new tumor marker and target for treatment. Here we made a comprehensive review on the role of ATP2A2 in tumorigenesis, and it is believed that the abnormal expression of ATP2A2 can damage the calcium homeostasis between cytosol and sarco (endo) plasmic reticulum, accelerating malignant proliferation, migration and angiogenesis of the tumor. Moreover, we also discussed the prospect of research and application of ATP2A2.