Identifying the factors influencing heavy metal contents in soil could reveal the pollution sources of heavy metals, and can lead to pollution mitigation opportunities. In this study, Heishitou Town in Weining County was selected as the study area, the inductively coupled plasma mass spectrometry (ICP-MS) and high-definition X-ray fluorescence spectrometer (HDXRF) were used to determine soil heavy metal contents, and then the spatial distribution and influencing factors (including soil topographic factors and soil physiochemical properties) of soil heavy metals were analyzed in order to explore the applicability of HDXRF in assessing soil heavy metal pollution. The results show that both the contents of Cd, Pb, Zn, Cr, Cu and Ni determined by HDXRF and ICP-MS follow the normal distribution. Cu determined by HDXRF is about 16% higher than by ICP-MS, no significant difference is found in the determined contents of other elements but a significant correlation between the same heavy metals by ICP-MS and HDXRF, with the correlation coefficient ranged from 0.702 to 0.940 (P<0.01), and the similar results are found between the contents by ICP-MS and HDXRF and the influencing factors, in which, Cd, Pb, Zn, Ni significantly correlated with soil physiochemical properties, Cr significantly correlated with soil physiochemical properties, slope aspect and elevation, and Cu significantly correlated with cation exchange capacity (CEC) and elevation (P<0.01). The interactive detection results of geographical detector show that the interaction of influence factors has enhancement effect, the interaction between pH, organic matter, CEC and other factors are the dominant factors for the spatial differentiation of Cd, Pb and Zn, while spatial differentiation of Cr, Cu and Ni are resulted from soil physiochemical properties and terrain, with interaction value from 0.200 to 0.700. In conclusion, the accuracy and precision of HDXRF is good, and the spatial distribution of soil heavy metals is greatly influenced by the interaction of topography and soil physiochemical properties. HDXRF can be used for rapid detection and assessment of soil heavy metals, the variable models related to soil pH, organic matter and topographic factors should be established to correct systematically the results by ICP-MS.