The results demonstrated that the presence of pretreatment (hazard ratio [HR]: 2.995, 95% confidence interval [CI]: 1.040–8.620, p = 0.042), AFP (HR: 1.002, 95% CI: 1.001–1.002, p = 0.002), PIVKA-II (HR, 1.004; 95% CI, 1.002–1.006; p < 0.001), ALBI score (HR: 3.609, 95% CI: 2.342–5.562, p < 0.001), and SMI (HR: 0.941, 95% CI: 0.906–0.977, p = 0.001) were independent prognostic factors for advanced HCC patients treated with LEN/SOR. Here, AFP is linked to hepatocellular carcinoma.