Purpose To identify early biomarkers for the prediction of the therapeutic response in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) and sorafenib (referred to as TACE plus sorafenib) and establish an effective prognostic nomogram. Materials and Methods The study was approved by the institutional ethics review boards at both participating centers. This retrospective study included all patients with HCC who underwent TACE plus sorafenib therapy between January 2010 and December 2013 at two institutions. On the basis of the overall survival (OS), early biomarkers were identified with univariate and multivariate analyses; then, a prognostic nomogram was established and internally validated by using the concordance c statistic. Results Ninety-seven patients (mean age, 55.0 years; range, 27-89 years) were included. Of these patients, 84 (86.6%) were men. The median OS was 25.7 months. After univariate and multivariate analyses, the onset of sorafenib-induced hypertension and/or dermatologic adverse events (AEs) (grade ≥2) within the first month of sorafenib initiation were demonstrated as independent predictors of OS. The median OS of patients with either of the two independent risk factors was 32.2 months, which was significantly longer than for those patients without (19.8 months; P = .005). Survival analyses showed that the earlier the AEs (sorafenib-related dermatologic AEs or hypertension) occurred, the better the outcome of the combination therapy. A prognostic nomogram was established and showed high accuracy of the nomogram with the c statistic of 0.73. Conclusion The early onset of hypertension and/or sorafenib-related dermatologic AEs are early biomarkers for the clinical prognosis of patients with HCC treated with TACE plus sorafenib. © RSNA, 2017.