Background: Oral Squamous Cell Carcinoma (OSCC) is a malignant tumor that can rapidly infiltrate the oral epithelial tissue and cause high mortality worldwide because the available therapies are less effective. Chrysanthemum cinerariifolium leaf contains secondary metabolites as anti-inflammatory, antioxidant, anticancer, and antimutagenic. Aims: The study aimed to analyze the ethanolic extract of C. cinerariifolium leaf in reducing proliferation (Ki-67) and the degree of dysplasia in OSCC rats. Methods: This study used male Sprague Dawley induced by DMBA 0.5% and divided into five treatment groups, namely positive control/C+ (sick), negative control/C- (healthy), and treatment group generated with DMBA and given extract C. cinerariifolium leaf with successive doses of T1, T2, and T3 (50, 100 and 200 mg/k g bw). The oral epithelium was stained with hematoxylin and eosin and immunohistochemically stained with a Ki-67 monoclonal antibody. Statistical analysis utilizing One-Way ANOVA. Results: The results showed that T1 at a dose of 200 mg/kg bw could significantly reduce Ki-67 expression and the degree of oral epithelial dysplasia (p<0.05) close to healthy controls. Conclusion: The conclusion shows that C. cinerariifolium leaf extract can be a therapy against OSCC by decreasing cell proliferation and the degree of oral epithelial dysplasia.