Objective: To study the effect of Guizhi Fuling Pill combined with gonadotropin-releasing hormone analog (GnRH-a) on cell proliferation and invasion as well as MEK/ERK pathway in endometriosis lesions. Methods: Patients who were diagnosed with endometriosis in Bazhong Hospital of Traditional Chinese Medicine between November 2014 and March 2017 were selected as the research subjects and randomly divided into two groups, observation group received preoperative Guizhi Fuling Pill combined with GnRH analog therapy, and control group received preoperative GnRH analog monotherapy. After surgical resection, the endometriosis lesion was collected to determine the mRNA expression of proliferation and invasion-related genes as well as the protein expression of MEK/ERK pathway molecules. Results:Id-1, Sema3A, c-IAP1, OPN and uPA mRNA expression as well as p-MEK, p-EKR1/2, caspase-3 and MMP2 protein expression in endometriosis lesion of observation group were significantly lower than those of control group while Bak, Smac, PAI-1, TIMP1 and TIMP2 mRNA expression as well as caspase-3 protein expression were significantly higher than those of control group. Conclusion: Guizhi Fuling Pill combined with GnRH analog can inhibit the cell proliferation and invasion as well as the MEK/ERK pathway activation in endometriosis lesions.