Objective To evaluate the effectiveness of anti-pressure protective mask for medical personnel fighting against the coronavirus disease 2019 (COVID-19). Methods Convenience sampling method was used to select 120 military frontline anti-epidemic medical personnel supporting Wuhan medical team from Jan. 26 to Feb. 24, 2020, and they were evenly divided into blank group, control group and observation group. The blank group did not use anti-pressure dressings, the control group wore face protection equipments after using hydrocolloid dressings, and the observation group wore face protection equipments after using anti-pressure protective mask. At the end of the intervention, the facial comfort, facial pressure injuries, and adverse effects were compared between the three groups. Results At the end of the intervention, the facial comfort score was 6.00 (6.00, 7.00) in the blank group, 5.00 (4.00, 5.00) in the control group, and 1.00 (0.50, 2.00) in the observation group, with significant differences found among the three groups (H=97.392, P<0.001). According to the further inference of the rank mean, the blank group had the largest facial comfort rank mean (96.68), while the observation group had the smallest facial comfort rank mean (20.88). At the end of the intervention, three cases (7.5%, 3/40) in the blank group had no facial injury, 28 cases (70.0%, 28/40) had facial pressure injury at stage 1, and nine cases (22.5%, 9/40) at stage 2; 27 cases (67.5%, 27/40) in the control group had no facial injury and 13 cases (32.5%, 13/40) had facial pressure injury at stage 1; 37 cases (92.5%, 37/40) in the observation group had no facial injury and three cases (7.5%, 3/40) had facial pressure injury at stage 1. There was significant difference in the incidence of facial pressure injuries among the three groups (χ²=71.863, P<0.001). The observation group had the lowest facial pressure injury rate among the three groups. There was no skin allergic reaction in the three groups and none of them was infected with COVID-19. Conclusion Anti-pressure protective mask can effectively reduce the incidence of facial pressure injuries and improve the facial comfort when wearing facial protective equipment, and it can be used for protecting frontline anti-epidemic medical personnel.