Abstract: Porcine reproductive and respiratory syndrome virus (PRRSV) remains one of the most consequential pathogens threatening the sustainable development of the global swine industry. Its high genetic variability, capacity for persistent infection, and pronounced immune evasion continue to undermine the effectiveness of existing vaccines and conventional biosecurity-based control measures. As insight into host-virus interactions has deepened, host-directed strategies based on the identification of resistance genes have emerged as an increasingly important direction in PRRS research. In recent years, leveraging technologies such as transcriptomics, proteomics, genome-wide association analysis, RNA interference and CRISPR-based genome editing have enabled the identification of a growing set of key host factors involved in receptor recognition, viral entry, replication control and innate immune responses. Studies involving CD163, including whole-gene knockout, deletion of key domains, precise exon editing, and site-specific substitution, have demonstrated that genetically edited pigs expressing CD163 exhibit a relatively stable phenotype of resistance to PRRSV infection, thereby providing a new technical approach for disease-resistant breeding in pigs. Here we systematically reviewed recent strategies for identifying PRRSV host resistance genes and the major advances in this field, with a particular focus on the status, antiviral efficacy and translational prospects of CD163-edited pigs. We also discussed the challenges that remain, including biological safety, genetic stability and the potential for viral adaptive evolution, with the aim of informing future work on PRRS control and disease-resistant breeding.