The benefits of sorafenib as first-line treatment and regorafenib as second-line treatment for HCC patients after recurrence to TACE is not yet adequately studied. Aim: To estimate the efficacy of sorafenib as first-line treatment and regorafenib as second-line treatment in patients with intermediate-stage HCC after recurrence to previous TACE treatment. Retrospectively, we estimated the efficacy of sorafenib and regorafenib administration (overall survival [OS] and time to disease progression [TTDP]) in 12 patients (Group A) with intermediate-stage HCC after recurrence to treatment with TACE (1-3 TACEs; median, 2). The results were compared with those of a similar historical group of 15 HCC patients treated only with TACE (Group B). There were no significant differences in disease characteristics between the two studied groups. The index of disease control for group A was 67.2% and the mean TTDP was 4.2 months during sorafenib administration. Regorafenib was administered when progression of HCC was observed. The OS was 31.2 months. For Group B, the index of disease control was 30.6% (P = .001), the mean TTDP was 2.3 months (hazard ratio, 0.44; Ρ < .01), and the OS was 13.4 months (hazard ratio, 0.57; Ρ < .001). The multivariate analysis revealed that the addition of sorafenib and regorafenib was the most important factor for OS and the prolongation of the TTDP. The administration of sorafenib and regorafenib seems to be an attractive therapeutic approach for patients with intermediate-stage HCC after recurrence to previous TACE treatment.