This study is the first to document an essential role of the cellular ERGIC-53 lectin in HBV’s pathogenic life cycle. ERGIC-53 acts in teamwork with selective components of the COPII machinery, encompassing Sec24A, Sec23B and Sar1, to drive HBV ER export. Viral SVP secretion bypasses the need of this trafficking factor, implicating that ERGIC-53 resembles a checkpoint for the spatiotemporal export pathway segregation of HBV viral and spherical subviral particles. The characterization of the HBV-ERGIC-53 interaction identifies a pathogen-derived N-glycan as a crucial but not exclusive ligand of the lectin. The fact that the loss of ERGIC-53 or its function is well-tolerated in humans renders this protein as an attractive cellular target for therapeutic antiviral intervention.