In order to evaluate the potential health risk to local public caused by water pollution in Jiangsu reach of the Huaihe River, various organic pollutants, including Polycyclic Aromatic Hydrocarbons (PAHs), Organochlorine Pesticides (OCPs) and some other Semi-Volatile Organic Compounds (SVOCs), were determined. Preliminary health risk assessment (HRA) was performed by calculating the probability that the concentrations of detected compounds exceeded HHCWO (Human Health Criteria for Consumption of Water and Organism) after Kolmogorov-Smirnov test. The probabilities of posing a risk higher than 10−6 for most potential carcinogens were greater than 0.5, and some even approximated 1. Further HRA for potential carcinogens was performed based on Monte Carlo simulation. Cumulative Risk Probability (CRP) was introduced to characterize risk. The result showed that 3,3′-dichlorobenzidine posed the highest risk. PAHs with 4 ∼ 6 rings and some OCPs, such as heptachlorepoxide, aldrin and o,p′-DDT, also posed relatively high risk. Generally, there was a high level of heath risk in the study area. The study validated the high cancer incidence rate in areas along the Huaihe River.