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The present investigation aims to determine the health risks of toxic uranium contamination in the drinking water of the Thoothukudi district. Two hundred and eighty-six samples were examined during the pre- and post-monsoon seasons and found the uranium concentration ranges from <0.2 to 167 ppb (mean 12, Standard deviation 21) (pre-monsoon) and <02 to 190 ppb (mean 13, Standard deviation 24) (post-monsoon). Geochemical modeling studies and the reducing nature of samples reveal that the uraninite mineral is under saturated conditions, and the least soluble U4O9 mineral species is predominantly distributed during both seasons. Statistical analysis provides that applying nitrogen and phosphate fertilizers may induce the dissolution of uranium minerals, which is responsible for elevated uranium in the collected samples. The calculated noncarcinogenic risk of uranium range from 0.005 to 8.09 (pre-monsoon) and 0.005 to 9.18 (post-monsoon). 15% (pre-monsoon) and 17% (post-monsoon) of the samples show a higher noncarcinogenic risk. The calculated cancer mortality and morbidity are within the permissible limit of 10−3, and the present health risk assessment of uranium is evident that the people from this district have the chemical toxicity of uranium than the carcinogenic risk due to drinking water. [ABSTRACT FROM AUTHOR]