Background: The timing of the combination of an antiangiogenic agent (apatinib) and an immune checkpoint inhibition inhibitor (camrelizumab) in patients with advanced hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE) is unclear. Therefore, this study aims to evaluate the efficacy and safety of TACE combined with camrelizumab and apatinib for advanced hepatocellular carcinoma (HCC), and to explore the timing of the combination therapy. Methods: The institutional Review Board approved our study and registered it in the Chinese Clinical Trial Registry (ChiCTR2000034155). Between June 2020 and January 2022, we prospectively recruited patients with unresectable HCC not receiving systemic therapy and randomly divided them into preoperative and postoperative medication groups according to the timing of drug administration. Patients in the preoperative medication group received camrelizumab 200 mg per 2 weeks intravenously and oral apatinib 250 mg/day orally prior to TACE. Patients in the postoperative medication group received the same dose of camrelizumab and apatinib after recovery of liver function following TACE. The primary endpoint of the study was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events. Results: A total of 33 patients were enrolled in this study. There were 15 patients in the preoperative medication group and 18 patients in the postoperative medication group. Median OS was significantly longer in the postoperative medication group than in the preoperative medication group (20 months vs. 12 months; P = 0.034). Patients in the postoperative medication group achieved a higher DCR than that in the preoperative medication group [17 cases (94.4%) vs. 10 cases (66.7%), P = 0.039] Multivariate Cox regression analysis showed that post-TACE combination of apatinib and camrelizumab provided better OS than pre-TACE combination drug therapy (HR = 0.353, 95% CI:0.131-0.953, P = 0.040). No serious adverse events were observed in the two groups. Conclusions: TACE combined with apatinib and camrelizumab treatment in the patients with advanced HCC showed promising efficacy and a manageable safety profile. Compared to pre-TACE with apatinib plus camrelizumab, post-TACE with apatinib plus camrelizumab significantly improved OS and DCR in patients with advanced HCC. Clinical trial information: ChiCTR2000034155.