Objective To assess the association of zinc (Zn) with coal-burning endemic fluorosis (coal-burning fluorosis), so as to provide an evidence for the role of Zn in preventing coal-burning fluorosis. Methods Fifty children with dental fluorosis and 100 healthy controls were selected from Wushan County by stratified sampling, and the same number of children and controls were also selected from Fengjie County. Thirty adults were selected from skeletal fluorosis patients in Duping Township of Wushan County, and 60 healthy controls were selected in the same township. Fasting blood samples were collected from all the participants for Zn determination. Urine samples were collected to examine urine fluoride content. Wilcoxon rank sum test was used to analyze the differences in Zn and fluoride contents between cases and controls and between the two counties. The association between blood Zn and urine fluoride was examined by Pearson linear correlation/Spearman rank correlation. Results The average urine fluoride contents were significantly higher in the child fluorosis cases than in the controls from both counties (P<0.01); and the average blood Zn contents were significantly lower in the fluorosis cases than in the controls from both counties (P<0.01). Moreover, the child cases and controls from Wushan County had significantly lower average blood Zn contents compared with those from Fengjie County (P<0.05); the child fluorosis cases in Wushan County had a significantly lower urine fluoride content compared with those from Fengjie County (P<0.05). The average urine fluoride content of skeletal fluorosis adults from Wushan County was significantly higher than that of controls, and the average blood Zn content was significantly lower than that of controls (P<0.01). In addition, Pearson linear correlation/Spearman rank correlation showed a weak positive relationship between blood Zn and urine fluoride in both children and adults (P<0.05, P<0.01). Conclusion It is indicated that patients with fluorosis are generally Zn deficient, suggesting Zn deficiency might be a risk factor for fluorosis.