The human health risks caused by heavy metal contamination (As, Cd, Cr, Cu, Hg, Pb, Ni, and Zn) in the surface water of the Houjing River, the most contaminated river in southern Taiwan, were assessed in this study. Firstly, heavy metal contamination was evaluated by the contamination factors (CF) and the metal indexes (MI). Secondly, the human health risks due to heavy metal contamination were simulated using the Adaptive Risk Assessments Modeling System (ARAMS) through three scenarios; fish ingestion, dermal water contact, and incidental water ingestion during swimming. The hazard quotient (HQ) and the hazard index (HI) were used to evaluate non-carcinogenic risks, while carcinogenic risks were estimated by the lifetime cancer incidence risk index (CR) and the cumulative cancer risk (CCR). The results showed that the synergistic contamination of heavy metals in the surface water was severe (MI = 12.4), with the highest contribution from Cu, Ni, and Pb. Copper had the highest non-carcinogenic risk at the “adverse effect” level, while Ni and Cr had the highest carcinogenic risk at an “unacceptable” level. In addition, the cumulative risks of fish ingestion (HIFI = 6.75 and CCRFI = 1.25E-03) were significantly higher than those of the swimming scenarios (HI(DC + WI) = 1.94E-03 and CCR(DC + WI) = 9.32E-08). The results from this study will be beneficial for immediate and future contamination control measures and human health management plans for this study area. This study has also demonstrated the effectiveness of using ARAMS in human health risk assessment. Display omitted •High heavy metal contamination in the Houjing River's surface water was reported.•Adaptive Risk Assessments Modeling System was effective in health risk assessment.•Copper and Nickel had the highest noncarcinogenic and carcinogenic risk, respectively.•Cumulative noncarcinogenic risk was classified as “adverse effect”.•Cumulative carcinogenic risk was classified as “unacceptable”.