||Despite the importance of high-resolution population distribution in urban planning, disaster prevention and response, region economic development, and improvement of urban habitant environment, traditional urban investigations mainly focused on large-scale population spatialization by using coarse-resolution nighttime light (NTL) while few efforts were made to fine-resolution population mapping. To address problems of generating small-scale population distribution, this paper proposed a method based on the Random Forest Regression model to spatialize a 25 m population from the International Space Station (ISS) photography and urban function zones generated from social sensing data—point-of-interest (POI). There were three main steps, namely HSL (hue saturation lightness) transformation and saturation calibration of ISS, generating functional-zone maps based on point-of-interest, and spatializing population based on the Random Forest model. After accuracy assessments by comparing with WorldPop, the proposed method was validated as a qualified method to generate fine-resolution population spatial maps. In the discussion, this paper suggested that without help of auxiliary data, NTL cannot be directly employed as a population indicator at small scale. The Variable Importance Measure of the RF model confirmed the correlation between features and population and further demonstrated that urban functions performed better than LULC (Land Use and Land Cover) in small-scale population mapping. Urban height was also shown to improve the performance of population disaggregation due to its compensation of building volume. To sum up, this proposed method showed great potential to disaggregate fine-resolution population and other urban socio-economic attributes.