Abstract: To explore the spatiotemporal characteristics of habitat quality and its influencing factors on a large regional scale, the multi-source datasets, including land use/cover, meteorological, and socio-economic datasets were integrated. The InVEST model and spatial autocorrelation are employed to quantify and analyze the spatial pa-ttern of habitat quality in Guangdong Province from 2000 to 2020. Furthermore, the Geodetector is used to examine the influences of both natural and anthropogenic factors on the province's habitat quality. The results show that: (1) The habitat quality in Guangdong Province exhibits a spatial pattern of a gradual increase from the center to the periphery and from the coast to the inland, with significantly positive spatial autocorrelation and distinct differences in the spatial pattern of hot and cold spots. (2) The habitat quality in Guangdong Province from 2000 to 2020 undergoes a fluctuating change of "decreasing, then increasing, then decreasing". The habitat quality continuously declines in the Pearl River Delta region, while the Northern Ecological Development Zone and the Eastern Wing of the Coastal Economic Belt display a similar fluctuating trend, and the Western Wing of the Coastal Economic Belt shows an initial improvement followed by a decline. (3) The explanatory power of various influencing factors on habitat quality in Guangdong Province, denoted by q values, is ranked from highest to lowest as follows: population density, NDVI, GDP, road density, elevation, slope, annual precipitation, and annual mean temperature, and there is an interaction-enhancing effect among these influencing factors.