Mitosis and homeostasis depend on proper cellular morphological transformation and plasma membrane structure during interphase. PTEN is a tumor suppressor protein involved in cellular homeostasis and genomic stability. We have previously shown that loss of PTEN leads to impairment of mitotic spindle architecture and cytokinesis. Here we report a potential relationship between PTEN and actin in controlling cellular morphology. PTEN depletion results in disorganization of the actin cytoskeleton. This is manifested by decreased parallel alignment of actin filaments, increased F-actin at the membrane, and cells appeared rounder. We also found that Moesin (Moe), an actin-binding ERM protein involved in membrane morphology, exhibits greater level in the phosphorylated Moe (pMoe) form and dislocation of pMoe from the cell cortex. Using an inhibitor of actin polymerization in PTEN-deficient cells, our data show a reduced quantity of pMoe and the recovery of its membrane enrichment. Moreover, inhibition of actin polymerization also reduces F-actin at the membrane and the frequency of cells with round shape. These data suggest that PTEN may regulate cortical actin polymerization to maintain cellular morphology and membrane dynamics.