Runoff, which is a key component in the hydrological cycle, is mainly controlled by climate factors and land-surface elements in non-humid regions. The impacts of climate and vegetation changes on runoff based on Budyko hypothesis in the middle and upper reaches of the Pearl River Basin was analyzed in this article. First, the temporal trend of variables in the study area during 1981-2013 was examined by using the Mann-Kendall trend test with trend-free pre-whitening. Second, the relationship of the parameter n in Fu's equation with factors of climate and vegetation coverage was built to reveal the time-variation process of n. Finally, the effects of climatic factors and vegetation coverage on runoff were assessed by analyzing the sensitivity of runoff to each variable. It is found that average temperature (T), maximum temperature (T_max) and minimum temperature (T_min) in the study area present an increasing trend while runoff (Q), precipitation (P), wind speed (u₂) and relative humid (RH) present decreasing trend. The parameter n in Fu's equation is significantly related to both climatic factors (including precipitation (P), average temperature (T), relative humid (RH), sunshine duration (S), wind speed (u₂)) and vegetation coverage index (NDVI). In terms of sensitivity of Runoff (Q) to the variation of each climatic factors and NDVI in the middle and upper reaches of the Pearl River Basin, precipitation (P) and NDVI have the highest sensitivity, followed by other climatic factors. Additionally, the precipitation (P) reduction is the main driving factor to the decline in runoff, while vegetation coverage is another important factor. In general, climate change affects runoff not only by changing the hydrological inputs (precipitation (P) and potential evaporation (PET) but also by altering the watershed characteristics as represented by the parameter n, while the impacts of vegetation coverage on runoff are exerted mainly through the alteration of the watershed characteristics.