Abstract: Objective: Exploring the disinfection effect of high-pressure carbon dioxide (HPCD) on human coronavirus 229E (hCoV-229E). Methods: The human coronavirus 229E (hCoV-229E) was treated by HPCD at different temperatures (10, 25, and 37 ℃) and pressures (6.3 and 10 MPa) for different time (15 and 30 min). Result: Compared with the control groups under the corresponding temperatures, the virus titer in 50 mL tube treated with HPCD at 10 ℃ and 6.3 MPa for 30 min was significantly decreased (P<0.05). The virus titer was also significantly reduced after treatment with HPCD at 37 ℃ and 10 MPa for 15 min (P<0.01). Moreover, the virus titers inoculated on the surfaces of salmon meat, shrimp shell, and polyethylene packing materials were all significantly decreased after HPCD treatment at 37 ℃ and 10 MPa for 15 min as compared with the corresponding control groups (P<0.05). Conclusion: HPCD treatment at 37 ℃ and 10 MPa for 15 minutes could effectively disinfect hCoV-229E on the surface of food (salmon meat and shrimp shell) and polyethylene packaging materials.