Summary: The concentration of fluoride (F) in groundwater samples of district Tharparkar was determined, which is the largest arid region of Sind province. Various other water quality parameters such as pH, EC, TDS, Ca, Mg, Na, K, Cl, SO4, HCO3, were also measured. On the basis of these results, the groundwater of dist. Tharparkar can be characterized according to Rabinove, et al., classification of salinity as moderately to highly saline and according to Durfor, Beaker’s classification of total hardness, these samples may be characterized as hard to very hard. A systematic calculation of correlation coefficient among fluoride and other physicochemical parameters was performed, a significant –ve correlation was observed for F and Ca, Ca/ F ratio, Mg, HCO3, & Cl contents of district Tharparkar. The fluoride concentration in the groundwater samples of this region varied from (0.93–11.8) mg/ L. 27 samples out of 33 were found to have higher fluoride contents as compared to WHO Guideline value of 1.5 ppm. These elevated levels of fluoride are putting the population at a high risk of dental and skeletal fluorosis and other severe problems associated with fluoride.