Background: The combination of immune checkpoint inhibitors (ICI) and vascular endothelial growth factor (VEGF) antibodies manifested high efficacy in advanced hepatocellular carcinoma (HCC), which still needs to be further verified. We aimed to evaluate the safety and activity of this strategy with different doses, as well as to explore potential predictive biomarkers. Methods: In this two-part phase Ib study, patients with advanced or metastatic HCC were enrolled. Part 1 was dose escalation trial with sintilimab plus bevacizumab biosimilar (IBI305) 7.5 mg/kg (initial dose) or 15 mg/kg (escalated dose). Part 2 was extension in each tolerable dose group. Peripheral blood samples and tumor tissue specimens were collected before treatment to detect serum cytokines and tumor immune microenvironment (TiME) by multiplexed bead immunoassays and multicolor immunofluorescence. Results: Fifty patients were enrolled in final analysis. Among all, IBI305 7.5 mg/kg was administered in 29 patients and 21 patients with 15 mg/kg. The most common adverse event suspected to be treatment-related was hypertension (32%), proteinuria (26%) and fever (26%). The incidence of the grade 3-5 adverse events in group 15 mg/kg was 28.6%, while 13.8% in 7.5 mg/kg group. Overall, the ORR was 34% (17/50) and the DCR reached to 78% (39/50). The median PFS was 10.5 months (95%CI, 8.4-12.7) and the median OS was 20.2 months (95%CI, 16.1 -24.3). The ORR for 7.5 mg/kg and 15 mg/kg were 31% and 38%, respectively. Further analysis showed that responder patients (CR+PR+SD≥12 weeks) had significantly higher level of serum CD137 than those with non-responder group (PD+SD≥12weeks) (median, 32.8 versus 19.8 pg/mL, P = 0.034). Patients with a high level of CD137 ≥ 31.8 pg/mL had longer PFS (mPFS:14.2 vs. 4.1months, P = 0.001) and OS (mOS: NR vs.15.6months, P = 0.023). In addition, the TiME analysis demonstrated that the density of M1 macrophages (CD68+CD163-) in stroma was related to efficacy (P = 0.033), longer PFS (P = 0. 024) and OS (P = 0.046). Conclusions: The sintilimab plus IBI305 is well tolerated and effective, IBI305 of 7.5 mg/kg could be also optional to some patients. The serum CD137 and M1 macrophages are potential predicting biomarkers for the combination therapy Clinical trial information: NCT04072679.