Estrogen exerts essential role in liver metabolism, and its deficiency is frequently accompanied by a series of metabolic disorder diseases. To investigate the role of estrogen deficiency in fluorine ions (F) induced liver injury, the ovariectomy (OVX) rat models were performed by surgically removing the ovaries, and the rats from OVX and non-OVX models were exposed to differential dose of F (0, 25, 50 and 100 mg/L) in drinking water for 90 days. The liver morphological structure was evaluated by hematoxylin-eosin staining. Proliferation ability of hepatocytes was evaluated by 5-bromo-2-deoxyuridine (BrdU) assay. And distribution of lipid droplets in liver tissue was observed via oil red O staining. In addition, the liver function and lipid metabolism parameters in serum were detected by commercial kits. Results showed that F induced hepatocytes morphological damage and inhibited the proliferation ability of hepatocytes; estrogen deficiency exacerbated these changes. The deposition of lipid droplets in the liver tissue was multiplicative with increased F dose, especially after estrogen deficiency. In addition, F exposure increased (P < 0.05 or P < 0.01) serum aminotransferase (ALT), aminotransferase (AST), alkaline phosphatase (ALP), and γ-glutamyl transpeptidase (γ-GT) activities and total bilirubin (T-bil) level; meanwhile, serum triglyceride (TG) and cholesterol (TC) levels were also elevated (P < 0.05 or P < 0.01). F-induced liver function and lipid metabolism indexes were further increased (P < 0.05 or P < 0.01) in the state of estrogen deficiency. In conclusion, estrogen deficiency aggravated F-induced liver damage and lipid metabolism disorder.