Seed plant diversity is under threat due to human over-exploitation and changes in land use. There is a need to identify regions where seed plant diversity is most at risk and establish nature reserves to protect the most important species. This study collected province scale seed plant richness data and corresponding environmental, social and, economic data in China in order to assess the impact of environmental and socio-economic factors on seed plant diversity and to quantify the relative importance of climate, human disturbance, and habitat heterogeneity on the distribution of seed plant diversity. A downscaling model was established to map the spatial distribution of seed plant diversity at a 1-km resolution. The results showed that temperature and precipitation seasonality, potential evapotranspiration, humidity index, altitude range, and gross domestic product were important determinants of seed plant diversity. The relative contribution of temperature seasonality was the most important factor (explaining 29.9–36.2% of the variation). Climate, human disturbance, and habitat heterogeneity explained much of the seed plant richness and density variation (about 69.4–71.9%). A scale-down model explained 72% of seed plant richness variation and showed that the center of seed plant species diversity was mainly located in the southeast area of China in the Qing-Tibet Plateau, Yun-Gui Plateau, Hengduan Mountain region, middle of the Sichuan Basins, Taiwan island, and Hainan island. This study improves our understanding of biodiversity hotspot regions and is a useful tool for biodiversity conservation policy and nature reserve management in China.