Climate and land use changes have a significant impact on the hydrological cycle in river catchment and water resources in several regions of the world. This study used Coupled Model Intercomparison Project Phase 6 (CMIP6) output and the Soil and Water Assessment Tool (SWAT) model for analyzing the simultaneous effects of land use and climate changes on the hydrological response and runoff of the Bojnourd catchment in Iran. First, the changes in climatic parameters during 2020-2050 were investigated, using the Coupled Model Intercomparison Project Phase 6 (CMIP6). Thus, the scenarios of Shared Socioeconomic Pathways (SSP245) and (SSP585) were applied to predict temperature and precipitation. Also, the land use changes were analyzed for 2001 and 2019 and predicted for 2040, by using the Environment for Visualizing Images (ENVI) based on the CA-Markov model. Besides, the Sequential Uncertainty Fitting (SUFI2) algorithm is used for validation of the SWAT hydrological model. The results show that the land use model is accurate (Kappa coefficient of 0.91 and 0.95) and the hydrological model is acceptable, as the Nash-Sutcliffe (NS) coefficient in the calibration stage was 0.59 and in the confirmation stage it was 0.50 percent. The results indicate that between 2001 to 2040, the residential area has increased from 2.6 to 6 percent, and the barren area will increase from 23 to 27 percent, instead the rangeland will decrease from 59 to 47 percent. Generally, the precipitation will decline and the temperature will increase in the region. As a consequence, in both scenarios, the runoff decreases, while the land use change will cause a slight increase in the runoff, however, this increase is less than the decreased effect of climate change. The study helps to understand and manage the effects of climate change and land use change on water resources.