<p>As the primary alternatives to brominated flame retardants, chlorinated organophosphorus flame retardants (Cl-OPFRs) have seen surging production and usage. Consequently, they are now widely distributed and persistent in indoor dust, air, water, and food. These pollutants accumulate in human samples and pose significant hazards to living organisms, with increasing evidence identifying the liver as the main target organ. This paper systematically summarises current progress regarding the absorption and metabolic fate of Cl-OPFRs and reviews their hepatic effects. We propose that Cl-OPFRs induce liver damage through multiple pathways: oxidative stress, inflammatory responses, lipid metabolism disruption, mitochondrial dysfunction, gut-liver axis disruption, cell cycle arrest, and apoptosis. Importantly, these mechanisms function synergistically rather than in isolation. Core drivers, particularly oxidative stress and mitochondrial dysfunction, engage in complex interactions that form positive feedback loops, collectively amplifying liver injury. Despite these advances, current research is constrained by the discrepancy between high-dose experimental models and real-world exposures, as well as limited metabolite data. Future research should prioritise environmentally relevant chronic models and investigate non-apoptotic cell death (e.g., ferroptosis), sex-specific vulnerabilities, and metabolite toxicity. In conclusion, this review provides an outlook for future research and offers scientific evidence to support the rational application of Cl-OPFRs and the mitigation of their environmental health risks.</p>