Rodents often act as keystone species in communities and play important roles in shaping structures and functions of many ecosystems. Understanding the underlying mechanisms of population fluctuation in rodents is therefore of great interest. Using the data from a 25-year field survey carried out in Inner Mongolia, China, we explored the effects of density dependence, local climatic factors, and a large-scale climatic perturbation (El Niño–Southern Oscillation) on the population dynamics of the striped hamster (Cricetulus barabensis), a rodent widely distributed in northern China. We detected a strong negative density-dependent effect on the population dynamics of C. barabensis. Rainfall had a significant positive effect on population change with a 1-year lag. The pregnancy rate of C. barabensis was negatively affected by the annual mean temperature in the current year, but positively associated with the population density in the current year and the annual Southern Oscillation Index in the previous year. Moving-window analyses suggested that, with a window length of 12 years, there was a significant interaction between rainfall and density dependence, with increasing rainfall alleviating the negative effect of density dependence. As C. barabensis often causes agricultural damage and can transmit zoonotic diseases to human beings, our results also have implications for pest and disease control.