Objective To explore the effect of negative pressure wound therapy (NPWT), drip irrigation with Compound Cortex Phellodendri (CCP) fluid, and topical oxygen therapy in management of stage 3 to 4 pressure injury.Methods A total of 98 patients with stage 3 to 4 pressure injury were randomized into two groups, with 49 in each group.The control group was given NPWT and drip irrigation with normal saline, while the observation group received NPWT, drip irrigation with CCP fluid, and topical oxygen therapy.The Pressure Ulcer Scale for Healing (PUSH) score, treatment effect, length of hospital stay, and serum inflammatory cytokines were assessed before and at 2, 4 weeks after initiation of the treatment.Results At 2 and 4 weeks after ini-tiation of the treatment, the PUSH score, C-reactive protein value, interleukin-6 concentration and length of hospital stay in the observation group were significantly lower/shorter than those in the control group （all P＜0.05）, and the treatment effect of the observation group was significantly better than that of the control group at 4 weeks after initiation of the treatment （P＜0.05）.Conclusion NPWT, drip irrigation with CCP fluid, and topical oxygen therapy for treatment of stage 3 to 4 pressure injury, can effectively reduce the concentrations of serum inflammatory cytokines, improve the healing rate and shorten the hospital stays.