AIM: To detect the expression of erythropoietin(EPO)and hypoxia-inducible factor-1α(HIF-1α)in serum and aqueous humor of patients with acute anterior uveitis(AAU), and to explore their clinical significance. METHODS: From January 2018 to December 2020, 60 patients with AAU in our hospital were prospectively selected as the research objects, and 60 patients with proliferative vitreoretinopathy in the same period were taken as control(control group). The serum and aqueous humor of two groups were collected, enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of EPO and HIF-1α in serum and aqueous humor; the self-rating anxiety scale(SAS)and the self-rating depression scale(SDS)were used to evaluate the AAU patients, and the severity of the disease was scored; Pearson method was used to analyze the correlation between SAS score, SDS score and levels of EPO and HIF-1α in serum and aqueous humor, and the correlation between levels of EPO and HIF-1α in the serum and aqueous humor. Spearman was used to analyze the correlation between the disease severity score of AAU patients and the levels of EPO and HIF-1α in serum and aqueous humor. RESULTS: Compared with the control group, the levels of EPO and HIF-1α in the serum and aqueous humor of the study group were higher(P<0.01). Among AAU patients, 23 were negative of SAS score and 37 were positive, and 29 were negative of SDS score and 31 were positive. Compared with patients with negative SAS score, the level of HIF-1α in serum and the level of EPO in the aqueous humor were higher in patients with positive SAS score(P<0.05); compared with patients with negative SDS score, the level of EPO in serum and the levels of EPO and HIF-1α in aqueous humor were higher in patients with positive SDS score(P<0.01). There were 26 mild patients and 34 severe patients with AAU. Compared with mild patients with AAU, the levels of EPO and HIF-1α in serum and aqueous humor were increased in severe patients(P<0.01). Pearson analysis showed that the SAS and SDS scores of AAU patients were not significantly correlated with the levels of EPO and HIF-1α in serum and aqueous humor(P>0.05), there was a positive correlation between EPO and HIF-1α in serum(P<0.05), and between EPO and HIF-1α in aqueous humor(P<0.05). Spearman analysis showed that the disease severity score of AAU patients was positively correlated with the levels of EPO and HIF-1α in serum and aqueous humor(P<0.05). CONCLUSION: EPO and HIF-1α are highly expressed in serum and aqueous humor of AAU patients, and they are closely related. The two are closely related to the disease severity score, and should be paid attention to clinically.