Objective:To explore the relationship between blood Zinc(Zn),Calcium(Ca),Copper(Cu),Magnesium(Mg) and Ferrum(Fe) levels and the incidence of coal-burning endemic fluorosis and to find effective anti-fluorine elements for the prevention and control of the disease. Methods:Stratified cluster random sampling method was used and 250 children and 90 adults were investi-gated in fluorosis area and non-fluorosis area for 1∶2 matched case-control study. Fasting venous blood samples were collected by venipuncture in vacuum tubes from all subjects and the concentrations of blood Zn,Ca,Cu,Mg and Fe levels were examined with atomic absorption spectrometer. Spot urine samples were collect-ed from all subjects and the fluoride levels were detected by fluoride ion selective electrode. Results:Blood Zn levels of Wushan children were (78.82±11.40) μmol/L in external con-trols,higher than (73.39±8.99) μmol/L in internal controls and (69.01±6.98) μmol/L in case group. Similarly,blood Zn levels of Fengjie children were (78.82±11.40) μmol/L in external controls,higher than (77.66±12.03) μmol/L in internal controls and (72.76±10.87) μmol/L in case group. Blood Zn levels of Wushan adults were (101.21±11.91) μmol/L in external controls,higher than (97.92±11.51) μmol/L in internal controls and (91.13±10.29) μmol/L in case group,all P<0.05. Blood Cu and Fe levels of children in Wushan and Fengjie were higher in external controls than in internal controls and case group,P<0.01. Urine fluorine were higher in case group than in internal and external controls in Wushan children and adults and Fengjie children,P<0.01. Concentrations of blood Zn,Ca and urine fluorine were (72.76±10.87) μmol/L,(1.82±0.19) mmol/L and (0.83±0.37) mg/L in Fengjie case group,higher than those of (69.01±6.98) μmol/L,(1.41±0.12) mmol/L and (0.65±0.33) mg/L in Wushan case group. Similarly,concentrations of blood Zn,Ca and urine fluorine were (77.66±12.03) μmol/L,(1.85±0.23) mmol/L and (0.53±0.23) mg/L in Fengjie internal controls,higher than those of (73.39±8.99) μmol/L,(1.45±0.21) mmol/L and (0.43±0.18) mg/L in Wushan internal controls,P<0.05 of blood Zn and urine fluoride,P<0.01 of blood Ca. Con-clusions:Blood concentration of Zn,Ca,Cu,Fe are closely related with the process of coal-burning endemic fluorosis in the two coun-ties except the main pathogenic element of fluorine. Patients with fluorosis have lower blood Zn levels and children have lower blood Cu and blood Fe in two counties. Concentrations of blood Zn and blood Ca are decreased with the increase of severity of endemic fluorosis.