Twelve perfluoroalkyl substances (PFASs) and nine organochlorine pesticides (OCPs) were quantified in surface sediments from the Huaihe River, China, along which there are intensive industrial and agricultural activities. Concentrations of PFASs ranged from 0.06 to 0.46 ng/g dry weight (dw), and concentrations of OCPs ranged from 1.48 to 32.65 ng/g dw. Compared with other areas in China, concentrations of PFASs were lesser than the national mean value, while concentrations of OCPs were moderate. Concentrations of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) ranged fromn.d. (not detected) to 0.03 and n.d. to 0.10 ng/g dw, respectively. Among the three groups of OCPs, mean concentrations of hexachlorocyclohexane and its isomers (HCHs), dichlorodiphenyltrichloroethane and its metabolites (DDTs) and hexachlorobenzene (HCB) were 5.62±4.35, 2.43±3.12 and 1.55±4.17 ng/g dw, respectively. Concentrations of HCHs and DDTs decreased from upstream to downstream along the mainstream of the Huaihe River. When compared to sediment quality guidelines (SQGs), concentrations of HCHs, DDTs and HCB would pose adverse biological effects. In general, contamination by PFASs in the upstream of the Huaihe River was more severe than that in the downstream, which was mainly caused by interception from dams, locks and industrial emissions. And OCPs fromtributaries, especially the Yinghe River andWohe River, were higher than those from Huaihe mainstream, and primarily came from historical inputs.