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Antibody-dependent enhancement (ADE) in porcine reproductive and respiratory syndrome virus (PRRSV) infection is a significant obstacle to the development of effective vaccines for controlling PRRS. Our previous results have demonstrated that porcine FcγRIIb (poFcγRIIb) play an important role in mediating ADE of PRRSV infection in vitro. However, the underlying mechanisms involved in poFcγRIIb mediated-ADE are still not clear. In this study, MARC-145 cel1 lines stably expressing mutated poFcγRIIb (MARC-poFcγRIIb-T and MARC-poFcγRIIb-CT) in cytoplasm were established and the capacity of poFcγRIIb mutants in mediating ADE of PRRSV was investigated. Our results showed that removal of cytoplasmic domain or disruption the tyrosine residue within ITIM (immunoreceptor tyrosine-based inhibition motif) of the poFcγRIIb abolished the ability of poFcγRIIb to mediate ADE of PRRSV. Furthermore, we found that SHIP1 and TBK1 were involved in poFcγRIIb-mediated ADE of PRRSV infection. Taken together, our findings indicated that poFcγRIIb mediated the ADE pathway of PRRSV infection through recruiting SHIP-1, which further inhibited of TBK-1-IRF3-IFN-β signaling pathway to enhance PRRSV infection. These findings will contribute to the molecular mechanism of ADE infection and provide some implications for vaccine development.