Hydrological simulation in areas lacking historical meteorological data is one of the limiting factors that hinders the development of watershed models and people’s understanding of water resources. We selected Manas River Basin as the research area, and simulated its hydrological process using CMADS and SWAT model. Then the simulated runoff was calibrated using SWAT-CUP. According to the parameter sensitivity analysis, parameter calibration and validation, NSE, R2 and PBIAS were selected for the evaluation. It is found that the final values of the 9 hydrological parameters are all in a reasonable range, and the three statistical indices are in the optimal range during calibration and verification period in the monthly and daily runoff simulation. The simulation value of the model is well fitted with the measured value, indicating that this model can be used for subsequent research and application. The results show that the CMADS and SWAT model is applicable to the reproduction of the hydrological process of Manas River Basin. The meteorological data provided by CMADS is of continuous time, with detailed type classification and high spatial resolution, which is beneficial to the construction of hydrological models with higher accuracy in areas lacking historical meteorological data.