The striatin-interacting phosphatase and kinase (STRIPAK) is the highly conserved complex, which gains increased attention in physiology and pathology process recently. However, limited studies reported the details of STRIPAK complex in cancers while some results strongly suggested it plays a vital role in tumorigenesis. Hence, we systematically analyzed the molecular and survival profiles of 18 STRIPAK genes to assess the value of STRIPAK complex across cancers. Our findings revealed the low frequencies of DNA aberrances and incomparable expression difference of STRIPAK genes between normal and tumor tissues, but they showed strong prognostic value in cancers, especially the liver hepatocellular carcinoma (LIHC) and kidney renal clear cell carcinoma (KIRC). Interestingly, STRIPAK genes were observed the opposite pattern of survival and expression in the above two cancer types. PPP2R1A and TRAF3IP3 were proposed as the oncogenic genes in LIHC and KIRC, respectively. The STRIPAK genes serve as oncogenes may due to the methylation heterogeneity. Taken together, our comprehensive molecular analysis of STRIPAK complex provides resource to facilitate the understanding of mechanism and utilize the potential therapies to tumors.