The influences of different land uses associated with human activities on soil quality and the redistribution of heavy metal in soil have been widely concerned. Surface soil samples were obtained to assess comprehensive soil quality in a typical red soil region of southern China, combining the heavy metal pollution evaluation with fertility evaluation. It can be learned from the results that the overall level of soil fertility was at medium and lower level, and soil heavy metal pollution risk in the study area in a few regions had reached warning line and slight pollution line, and there was a risk of potential pollution. TOPSIS evaluation results showed that the comprehensive soil quality was mainly good quality and moderate quality, accounting for 31.7% and 29.0% of the total land area, respectively. Positive matrix factorization (PMF) model results showed that transportation source contributes a lot in terms of Cd and Pb. As for Cr, natural source contributes 53.8%. In terms of Cu and Zn, agriculture source contributes 50.7% and 38.7%, respectively. In a word, the comprehensive soil quality assessment in red soil region of southern China provides an important basis for the scientific management and sustainable utilization of soil resources.