The noncanonical NF-κB signaling pathway is an important branch of NF-κB signaling. It is involved in regulating mul-tiple important biological processes, including inflammation and host immune response. A central adaptor protein of the noncanonical NF-κB pathway is NF-κB-inducing kinase (NIK), which activates the downstream kinase IKKα to pro-cess p100 to p52, thereby forming the RelB/p52 heterodi-mer to initiate the expression of target genes. Currently, many specific inhibitors and monoclonal antibodies target-ing or triggering this pathway are being developed and tested for various diseases, including cancers, autoimmune diseases, and virus infection. Given that aberrant activation of the noncanonical NF-κB pathway is frequently observed in various liver diseases, targeting this pathway may be a promising therapeutic strategy to alleviate liver inflamma-tion. Moreover, activation of this pathway may contribute to the antiviral immune response and promote the clear-ance of persistent hepatotropic virus infection. Here, we review the role of the noncanonical NF-κB pathway in the occurrence and development of different liver diseases, and discuss the potency and application of modulating the noncanonical NF-κB pathway for treatment of these liver diseases.