Perfluorinated compounds (PFCs) and organochlorine pesticides (OCPs) were analyzed in surface soils along the Huaihe River. Sixteen target PFCs and nine OCPs were quantified in soils from a region of intensive industrial and agricultural development. Concentrations of PFCs and OCPs ranged from less than the limit of detection (LOD) to 1.22 ng/g and 3.63 to 227 ng/g, respectively. Contamination by OCPs was more serious than that of PFCs, which was consistent with the fact that OCPs were widely used in agriculture of the district while there was no known production or application of PFCs in the study area. The predominant PFCs in soils were PFOA and PFOS with concentrations that ranged from <LOD to 0.20 ng/g and <LOD to 0.21 ng/g, respectively. Among the three groups of OCPs, average concentrations of HCHs, DDTs, and HCB were 4.7, 23.7, and 1.4 ng/g, respectively. Results of principal component analysis revealed relatively weak associations between concentrations of PFCs and those of OCPs, while concentrations of OCPs exhibited similar patterns of distributions. Among the mainstream and five tributaries, the highest concentrations of PFCs were observed along the Pihe River, while the highest concentrations of OCPs occurred along the Xifeihe River. In general, concentrations of PFCs were evenly distributed, while those of OCPs exhibited relatively greater spatial differences.