Abstract: Clarifying the environmental fate of pollutants is of great significance to pollution control and ecological risk assessment.Understanding the distribution, migration and transformation process of pollutants in the environment is helpful to formulate scientific and effective pollution prevention measures. The distribution and migration of four typical drugs and personal care products (PPCPs) in environmental multi-media in Gansu section of Weihe River were studied by means of the third-order multi-media fugacity model and field sampling analysis.  The results show that: (1) the differences between simulated and measured values of four kinds of PPCPs are within one order of magnitude, and the accuracy of the constructed model is good;(2) the main transport processes between environmental media calculated by the model are advection and degradation.  Advection is the main input and removal pathway of PPCPs in aqueous phase, diffusion from water to suspended matter and deposition from suspended matter to sediment are the main input pathways of PPCPs in suspended and sediment phases. DEET tends to degrade in suspension and diffuse more easily from sediment to water. CLD and ROX were more prone to sediment deposition than the other two PPCPs. TMP is mainly removed by degradation in suspended matter and sediment. (3) Sensitivity study results show that input concentration of pollutants, partition coefficient of organic carbon, advection input and output of aqueous phase, temperature, organic carbon content in suspended solids and sediments are the main parameters affecting model results. (4) Uncertainty analysis shows that the change of global parameters has little effect on the output of water body, but has great effect on suspended matter and sediment.  This study simulates the multi-medium fate of typical PPCPs in the water environment of Gansu section of Weihe River, which provides scientific basis for pollution control and ecological risk assessment, and is helpful to optimize pollution prevention measures and strengthen ecological environment and water resources protection.