In this study, we thoroughly analyzed spatial and temporal distributions of runoff and their relation with precipitation changes based on monthly runoff dataset at 25 hydrological stations and monthly precipitation at 127 stations in Guangdong Province, south China. Trends of the runoff and precipitation are detected using Mann–Kendall trend test technique. Correlations between runoff and precipitation are tested using Spearman’s and Pearson’s correlation coefficients. The results indicate that: (1) annual maximum monthly runoff is mainly in decreasing tendency and significant increasing annual minimum monthly runoff is observed in the northern and eastern Guangdong Province. In addition, annual mean runoff is observed to be increasing at the stations located in the West and North Rivers and the coastal region; (2) analysis of seasonal runoff variations indicates increasing runoff in spring, autumn and winter. Wherein, significant increase of runoff is found at 8 stations and only 3 stations are dominated by decreasing runoff in winter; (3) runoff changes of the Guangdong Province are mainly the results of precipitation changes. The Guangdong Province is wetter in winter, spring and autumn. Summer is coming to be drier as reflected by decreasing runoff in the season; (4) both precipitation change and water reservoirs also play important roles in the increasing of annual minimum monthly streamflow. Seasonal shifts of runoff variations may pose new challenges for the water resources management under the influences of climate changes and intensifying human activities.