Abstract: Objective To determine the role of cancer associated fibroblasts (CAFs) in the invasive behavior of pituitary adenoma. Methods Pituitary adenoma tissues were divided into invasive group (IPA) and non-invasive group (nIPA) according to pre-operative MRI and observations during surgery. Those tissues were cultured and CAFs were identified through α smooth muscle actin (α-SMA). The migratory and invasive ability of CAFs was tested with transwell migration and invasion assay. The expressions of α-SMA and matrix metalloproteinase (MMP)-9 from CAFs were determined by immunocytochemistry and Western blot. Results All cultured CAFs expressed α-SMA. No significant difference in migratory ability of CAFs was found between the IPA and nIPA tissues; however, CAFs from the IPA tissues had stronger invasive ability than those from the nIPA tissues ( P=0.010). Higher levels of MMP-9 expression were found in group IPA as compared with nIPA ( P=0.025). No significant difference in the expression of α-SMA was found between the two groups. Conclusion CAFs may promote invasive behavior by secreting more MMP-9, which may play a part in the invasive behavior of pituitary adenomas.