Objective:To investigate the clinical effect of hyperbaric oxygen (HBO) combined with agomelatine on elderly patients with depression, and its effect on the levels of myeloperoxidase (MPO) and fibroblast growth factor-22 (FGF-22) in serum.Methods:A total of 136 elderly patients with depression treated in the Geriatrics Department of Air Force Special Medical Center and Neurology Department of Jilin People′s Hospital from May 2017 to December 2019 were randomly divided into observation group ( n=68) and control group ( n=68) by random number table method. The control group was treated with agomelatine, and the observation group was treated with HBO on the basis of the treatment of the control group. The clinical effect and adverse reaction after treatment, and anxiety score, depression score, and the changes of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), MPO, and FGF-22 of the two groups were compared before and after treatment. Results:After 3 courses of treatment, the total effective rate (91.2%) in the observation group was significantly higher than that in the control group (77.9%), with statistically significant difference ( χ2=4.561, P<0.05). The anxiety scores measured by Hamilton Anxiety Rating Scale (HAM-A) and the depression scores of both groups were significantly reduced after treatment, and the anxiety score and depression score of the observation group were significantly lower than those of the control group, with statistically significant difference ( P<0.05). The levels of TNF-α, IL-1β, and MPO in both groups were all significantly reduced after treatment, while the FGF-22 level in both groups was significantly increased. The levels of TNF-α, IL-1β, and MPO in the observation group were significantly lower than those in the control group, while the FGF-22 level in the observation group was significantly higher than that in the control group, with statistical differences ( P < 0.05). Conclusion:HBO combined with agomelatine has a good clinical effect on elderly patients with depression by improving the symptoms of anxiety and depression, which is worthy of clinical popularization and application in clinic.