晚期肝细胞癌（HCC）的治疗方式发生了巨大变化，全身治疗是主要选择。然而，序贯治疗对预后的影响仍不清楚。这项回顾性研究纳入了 2009 年至 2022 年间开始全身治疗的患者。根据全身治疗开始情况将患者分为三组。比较了治疗线的数量、治疗效果和总生存期（OS）。使用Cox比例风险模型对预后因素进行多变量分析。总体而言，纳入了 336 名患者（第 1 期：2009-2013 年，n = 86；第 2 期：2014-2018 年，n = 132；第 3 期：2019-2022 年，n = 118）。观察到病毒性肝炎相关性 HCC 减少和非病毒性肝炎相关性 HCC 增加的显着病因学趋势。在第 1-3 阶段，接受超过 2 线治疗的患者比例逐渐增加（分别为 1.2%、12.9% 和 17.0%；p < 0.001），中位 OS 显着延长（14.3、16.8 和 31.0 个月） ；p < 0.001）。使用<3个线、第一线的不完全和部分反应、2b级或3级改良白蛋白-胆红素、肝内肿瘤数≥5、肝外转移、甲胎蛋白≥400ng/mL与较短 OS 相关的最强因素。序贯治疗有助于显着改善 HCC 预后，表明进展后序贯治疗对于更好的生存是值得的。

Treatment modalities for advanced hepatocellular carcinoma (HCC) have changed dramatically, with systemic therapy as the primary option. However, the effect of sequential treatment on prognosis remains unclear. This retrospective study included patients who began systemic therapy between 2009 and 2022. The patients were separated into three groups according to systemic therapy commencement. The number of therapy lines, treatment efficacy, and overall survival (OS) were compared. Multivariate analyses of the prognostic factors were analyzed using the Cox proportional hazards model. Overall, 336 patients were included (period 1: 2009-2013, n = 86; period 2: 2014-2018, n = 132; period 3: 2019-2022, n = 118). A significant etiological trend was observed with decreasing viral hepatitis-related HCC and increasing non-viral hepatitis-related HCC. Across periods 1-3, the proportion of patients who were administered >2 lines progressively increased (1.2%, 12.9%, and 17.0%, respectively; p < 0.001) and the median OS was significantly prolonged (14.3, 16.8, and 31.0 months; p < 0.001). The use of <3 lines, the non-complete and partial response of the first line, modified albumin-bilirubin at grade 2b or 3, an intrahepatic tumor number ≥ 5, extrahepatic metastasis, and alpha-fetoprotein at ≥400 ng/mL were the strongest factors associated with shorter OS. Sequential therapies have contributed to significant improvements in HCC prognosis, suggesting that sequential treatment post-progression is worthwhile for better survival.