Pharmaceuticals and personal care products (PPCPs) are commonly seen emerging organic contaminants in aquatic environments. The transects for the occurrence and distribution of 24 PPCPs along the middle and lower reaches of the Yellow River (Henan section) were investigated in this study. All 24 targeted compounds were detected in surface water, with concentrations in the range from not detected (ND) to 527.4ng/L. Among these PPCPs, caffeine is found to have the highest concentration and its detection frequency is 100%. The total PPCP concentration ranged from 136ng/L to 916ng/L (median, 319.5ng/L). Spatial analysis showed that the pollution level of PPCPs in the trunk stream was lower than that in most tributaries in the middle and lower reaches of the Yellow River (Henan section). The ecotoxicological risk assessment indicated that norfloxacin, azithromycin, estrone, and triclosan posed high risks to aquatic organisms (RQ > 1), roxithromycin and oxytetracycline imposed moderate risks (0.1≤ RQ < 1), and the tributary Jindi River had the highest mixed risk (MRQ = 222).