This study assesses the influence of the total organic carbon (TOC) content, chlorine quantity, water temperature, bromide ion concentration, and seasonal variations on trihalomethanes (THMs) formation potential (THMFP) in Dez River water in Iran. The water temperature and TOC content had a significant effect on THMFP. Further, the experimental results showed that increasing the concentration of bromide ions enhances the formation of dibromochloromethane and bromoform. It was found that the THMFP in Dez River water during summer times was relatively higher than 100 µg/L, maximum contaminant level for THMs in drinking water. By increasing the reaction time until 80 h, the THMFP was gradually increased and reached to 177.4 µg/L. The most abundant fraction of natural organic matter in the river was hydrophobic acid fraction (49.4 μg/L). Overall, our study demonstrated that however the THMFP of Dez River water was relatively high but a usual waterworks could effectively reduce THMFP.