Phosphatase and tensin homolog deleted on chromosome ten (PTEN), one of the mostly investigated tumor suppressor genes, has a close correlation with tumorigenesis. The activation of PI3K-AKT pathway caused by abnormal PTEN is one of the major mechanisms underlying tumor occurrence. Therefore, PTEN regulation is important for uncovering new mechanisms of tumor occurrence and establishing novel therapeutic strategies. The cellular PTEN regulations including transcriptional regulation, post-transcriptional modulation, post-translation modification and protein-protein interaction are reviewed in this paper.