Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently characterized oncoprotein involved in the progression of several human malignancies. The present study aimed to investigate the clinical significance and biological function of CIP2A in astrocytoma. CIP2A expression was analyzed in 135 archived astrocytoma specimens using immunohistochemistry. Of these specimens, 75 cases (55.6%) overexpressed CIP2A. The CIP2A overexpression was observed to be positively correlated with advanced tumor grade (P<0.001). siRNA-mediated knockdown of CIP2A was performed in A172 and U87 cell lines. MTT, colony formation and soft agar colony formation assays and Annexin V/propidium iodide analysis were performed to assess the role of CIP2A in cell proliferation and apoptosis. CIP2A depletion in the astrocytoma cell lines inhibited cell growth, reduced anchorage‑independent cell growth and increased apoptosis. In addition, CIP2A depletion increased caspase‑3 cleavage and downregulated c‑Myc, Bcl‑2 and phospho‑Akt expression. These results validate the role of CIP2A as a clinically relevant oncoprotein and establish CIP2A as a promising therapeutic target of astrocytoma.