Objective To analyze the effect of local oxygen therapy combined with recombinant bovine basic fibroblast growth factor（rb ⁃ bFGF）and negative pressure drainage（VSD）on chronic refractory wounds. Methods From October 2020 to October 2021，40 patients with chronic refractory wounds who were admitted to the Department of Plastic and Burn Surgery，The First Affiliated Hospital of Bengbu Medical College，were selected and randomly divided into control group and experimental group. The control group was treated with debridement and then with closed negative pressure drainage（VSD）combined with normal saline，while the experimental group was treated with local oxygen therapy combined with rb⁃bFGF lavage on the basis of the control group. The hospital⁃ ization time and cost，clinical efficacy，and NRS pain score were compared between the two groups，and the wound tissues were collected before operation，7 days after the operation to observe the histopathological changes （the number of inflammatory cells in the wound），and immunohistochemical staining of VEGF and HIF⁃1α expres⁃ sion. Results Compared with the control group，the experimental group had significantly shorter hospitalization time，lower hospitalization expenses，and less pain，and the differences were statistically significant（P < 0.05）. Compared with that in the control group，the number of inflammatory cells in the wound tissue of the experimental group was significantly reduced，showing statistical significance（P < 0.05）. The immunohistochemical staining of VEGF and HIF⁃1α in the wound tissue in the experimental group showed that the expression of VEGF was signifi⁃ cantly increased，but that of HIF⁃1α was decreased，and the differences were statistically significant（P < 0.05）. Conclusion The therapeutic effect of local oxygen therapy combined with rb⁃bFGF and VSD is significantly betterthan that of VSD combined with saline irrigation. Local oxygen therapy combined with rb⁃bFGF and VSD can signif⁃ icantly reduce HIF⁃1α，increase the expression of VEGF，and improve the microcirculation of the wound and the healing of the wound. It also helps to shorten hospital stay，and reduce the economic burden of the patients.