Abstract: Hepatocellular carcinoma (HCC) is one of the cancers with the highest incidence and mortality rates in China and often presents with insidious early clinical manifestations. This frequency results in the majority of patients being diagnosed at middle and advanced stage of the disease, thereby missing the opportunity for potentially curative surgical interventions. For patients who are ineligible for radical surgical resection, a variety of therapeutic approaches, including systemic antitumor therapy, local radiotherapy, interventional treatment, and liver transplantation, have been employed. Moreover, neoadjuvant therapies have transformed a subset of initially unresectable HCC cases into operable ones. Nevertheless, many patients fail to benefit from these treatments, underscoring the urgent need for novel therapeutic targets. Cancer-associated fibroblasts (CAFs), a principal component of the solid tumor microenvironment, play a pivotal role in the proliferation, migration, invasion, and treatment resistance of cancer cells. This review delineates the origins of CAFs and their mechanisms of action in the pathogenesis and progression of HCC and discusses potential therapeutic strategies targeting CAFs.