Interest in the potential human health of semi-volatile organic chemicals (SVOCs) in indoor and outdoor environments has made the exposure assessment and source appointment a priority. In this study, paired indoor and outdoor atmospheric fine particle (PM_2.5) samples were collected from 15 homes representing five typical urban cities in southern China. Four typical SVOCs, including 16 congeners of polycyclic aromatic hydrocarbons (PAHs), 13 congeners of organophosphorus flame retardants (OPFRs) and 8 congeners of polybrominated diphenyl ethers (PBDEs), as well as tetrabromobisphenol A (TBBPA) and its three debrominated congeners were analyzed. The highest total concentrations were found for OPFRs, followed by PAHs, PBDEs, and TBBPA. The indoor concentrations of two alkyl-OPFR isomers, tributylphosphate (TBP) and tris (2-butoxyethyl) phosphate (TBEP), were 4.3 and 11 times higher, respectively, than those of outdoors (p < 0.05). Additionally, the ratios of indoor to outdoor concentrations of alkyl-OPFR isomers varied greatly, suggesting that these compounds originated mainly from different household goods and products used in individual homes. The outdoor concentrations of PAHs and highly brominated PBDEs (BDE-209) typically exceeded the indoor concentrations. Significant correlations were also found between indoor and outdoor PM_2.5 samples for PAHs and BDE-209, indicating that outdoor sources such as vehicle exhausts and industrial activities strongly influence their atmospheric occurrence. Additionally, the concentrations of debrominated TBBPA derivatives were higher than those of TBBPA in over 33% of both indoor and outdoor air particle samples. Nevertheless, our results indicated that inhalation exposure to typical SVOCs posed no non-carcinogenic risks to the human body. Although we observed notable differences in the sources, occurrences, and distributions of typical SVOC congeners, more studies using matched samples are still needed to unambiguously identify important indoor and outdoor sources in order to accurately assess the contributions of different sources and the associated human exposure risks.