Abstract: Objective To investigate the expression of Yin Yang 1 (YY1) protein in human insulinoma and explore its clinical significance. Methods Nineteen pancreatic neuroendocrine tumor tissue were collected from patients treated in Nanfang Hospital between 2000 and 2014. The protein expression of YY1 in benign and malignant insulinoma tissues were detected by immunohistochemistry. Results Positive expression for YY1 protein was detected in both benign and malignant tumor tissues, but the malignant tissues had a significantly greater intensity of YY1 expression than the benign tissues (P=0.042). The intensity of YY1 expression was positively correlated with the nature of the tumor, and the insulinomas with high expressions of YY1 had significantly greater malignant potentials (P=0.037). Conclusion The high expression of YY1 protein is associated with the development of insulinima. YY1 may serve as a new tumor marker for detecting the malignant transformation of insulinoma.