Background: The prognosis for advanced hepatocellular carcinoma (HCC) is still very poor. This study aimed to explore the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with camrelizumab plus targeted therapy for the treatment of patients with advanced HCC. Methods: In this single-arm, prospective, real-world study, patients with intermediate-stage unresectable HCC who had a Child-Pugh score ≤ 7 and had not received prior systemic anti-cancer treatment would receive comprehensive treatment with TACE followed by immunotherapy with camrelizumab 200 mg every 3 weeks plus a tyrosine kinase inhibitor (TKI) agent selected from lenvatinib (12 mg/day for bodyweight ≥60 kg or 8 mg/day for bodyweight < 60 kg), sorafenib 400 mg twice-daily or donafenib 200 mg twice-daily until intolerable toxicity or disease progression. During the study treatment, patients assessed as eligible for resection would undergo surgery. The primary endpoint was objective response rate (ORR) assessed by an independent review committee per modified RECIST. Secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). Results: From September 2020 to November 2021, 49 patients were enrolled. Among them, 45 (91.8%) patients were male, 41 (83.7%) patients were aged ≤65 years, 30 (61.2%) patients had extrahepatic metastases, and 41 (83.7%) patients had HBV infection. The ORR and DCR were 69.4% (34/49) and 87.8% (43/49), respectively. Five (10.2%) patients were assessed as eligible for surgery, and one of them already received surgery successfully and achieved pathological complete response. The median OS was not reached, and the median PFS was 6.1 months (95%CI, 1.4 -10.8). After 3 months, the alpha-feto-protein decreased compared with before treatment (p < 0.05). All patients had adverse events (AEs) of any grade. The most common AEs were reactive cutaneous capillary endothelial proliferation (30, 61.2%), abdominal pain (25, 51.0%), thyroid dysfunction (20, 40.8%) and fever (18, 36.7%). The majority of treatment-related AEs (TRAEs) were mild or moderate. Grade 3 TRAEs occurred in 3 (6.1%) patients, grade 4 TRAEs occurred in 1 (2.0%) patient, and no deaths occurred. Conclusions: TACE combined with camrelizumab plus targeted therapy in the treatment of advanced HCC shows good efficacy in controlling tumor progression and may provide opportunity of resection. Clinical trial information: ChiCTR2000039508.