非酒精性脂肪性肝病（NAFLD）正在成为肝细胞癌（HCC）的重要危险因素，其患病率正在上升。尽管从 NAFLD 进展为 HCC 的机制尚未完全阐明，但肿瘤坏死因子-α (TNF-α) 和脂联素及其看似拮抗的相互作用可能有助于 NAFLD 相关 HCC 的病理生理学。 TNF-α最初的目的是预防肝癌，但在NAFLD的进展过程中，TNF-α会增加，因此，当NAFLD未得到解决时，长期来看可能会诱发肝癌。另一方面，脂联素有望发挥抗肿瘤作用，但在疾病进展过程中会减少，这一趋势可能有利于肝癌发生，但在疾病末期（即肝硬化和肝癌）时却相反地增加。这些观察结果使 TNF-α 和脂联素成为 NAFLD 相关 HCC 中潜在的诊断生物标志物和有吸引力的治疗靶点，可能与系统治疗相结合。在这方面，联合策略，包括免疫检查点抑制剂 (ICIs) 与抗 TNF 生物制剂和/或脂联素类似物或增加内源性脂联素的药物，可能值得针对 NAFLD 相关 HCC 进行研究。本综述旨在根据实验和临床研究总结 TNF-α 和脂联素与 NAFLD 相关 HCC 之间关联的证据，并讨论相关的潜在治疗考虑因素。

Nonalcoholic fatty liver disease (NAFLD) is emerging as an important risk factor for hepatocellular carcinoma (HCC), whose prevalence is rising. Although the mechanisms of progression from NAFLD to HCC are not fully elucidated, tumor necrosis factor-α (TNF-α) and adiponectin, as well as their interplay, which seems to be antagonistic, may contribute to the pathophysiology of NAFLD-associated HCC. TNF-α initially aims to protect against hepatocarcinogenesis, but during the progression of NAFLD, TNF-α is increased, thus probably inducing hepatocarcinogenesis in the long-term, when NAFLD is not resolved. On the other hand, adiponectin, which is expected to exert anti-tumorigenic effects, is decreased during the progression of the disease, a trend that may favor hepatocarcinogenesis, but is paradoxically increased at end stage disease, i.e., cirrhosis and HCC. These observations render TNF-α and adiponectin as potentially diagnostic biomarkers and appealing therapeutic targets in the setting of NAFLD-associated HCC, possibly in combination with systematic therapy. In this regard, combination strategy, including immune checkpoint inhibitors (ICIs) with anti-TNF biologics and/or adiponectin analogs or medications that increase endogenous adiponectin, may warrant investigation against NAFLD-associated HCC. This review aims to summarize evidence on the association between TNF-α and adiponectin with NAFLD-associated HCC, based on experimental and clinical studies, and to discuss relevant potential therapeutic considerations.