Objective To explore the associations of the levels of miR-92a-3p and miR-206 with the positivity of inhibitors in patients with hemophilia A (HA), and to provide theoretical support for the clinical treatment and prognosis prediction of HA.Methods A total of 308 patients with HA admitted to our hospital from September 2020 to September 2024 were selected and divided into the positive group (64 cases) and the negative group (244 cases) according to the results of inhibitor detection. Clinical data such as the patient's sex, age, ethnicity, family history of HA, and treatment methods were collected. The levels of miR-92a-3p and miR-206, as well as the levels of serum tumor necrosis factor -α (TNF-α) and interleukin-6 (IL-6) in the patients were detected. Pearson analysis was used to evaluate the correlations between the levels of miR-92a-3p and miR-206 and the levels of inflammatory factors. Spearman analysis was used to evaluate the correlations between the levels of miR-92a-3p and miR-206 and inhibitor positivity in patients with hemophilia A. The logistic regression model was used to analyze the risk factors for the positivity of inhibitors in patients with HA.Results The proportion of preventive treatment in the negative group was higher than that in the positive group (P 0.05). The level of miR-92a-3p in the negative group was lower than that in the positive group (P 0.05), and the level of miR-206 in the negative group was higher than that in the positive group (P 0.05). The levels of TNF-α and IL-6 in the negative group were lower than those in the positive group (P 0.05). Pearson correlation analysis demonstrated that the levels of miR-92a-3p were positively correlated with the levels of TNF-α and IL-6 (r = 0.311 and 0.338, both P 0.05), and that the levels of miR-206 were negatively correlated with the levels of TNF-α and IL-6 levels (r = -0.424 and -0.249, P 0.05). Spearman correlation analysis revealed that the levels of miR-92a-3p were positively correlated with the positivity of inhibitors in HA patients (r_s = 0.372, P 0.05), and that the levels of miR-206 were negatively correlated with the positivity of inhibitors in HA patients (r_s = -0.509, P 0.05). The multivariable logistic regression analysis (P = 0.05 for including variables) showed that higher levels of miR-92a-3p [O^R = 1.185 (95% CI: 1.029, 1.365) ] and on-demand treatment [O^R = 1.342 (95% CI: 1.058, 1.701) ] were both risk factors for the positivity of inhibitors in HA patients (P 0.05), and that high levels of miR-206 [O^R = 0.840 (95% CI: 0.735, 0.960) ] were a protective factor for the positivity of inhibitors in HA patients (P 0.05).Conclusion Both miR-92a-3p and miR-206 are associated with inhibitor positivity in patients with HA. Elevated levels of miR-92a-3p and decreased levels of miR-206 are among the factors influencing inhibitor positivity in these patients.