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Background: Obsessive-compulsive disorder is a psychiatric disorder with different clinical manifestations caused by the interaction of genetic and environmental factors. Recently, it has been shown that microRNAs play a role in the pathogenesis of some psychiatric diseases. We aimed to compare the expression levels of microRNAs between obsessive-compulsive disorder patients and healthy controls and investigate the association between miRNA expression levels and treatment resistance., Methods: Twelve miRNA expression levels in venous blood of 100 obsessive-compulsive disorder patients and 50 healthy controls were detected by real-time polymerase chain reaction. Patients were assessed using the Hamilton Depression Rating Scale, Yale-Brown Obsessive-Compulsive Scale, and Yale-Brown Obsessive-Compulsive Symptom Checklist. Each patient was scheduled for a monthly follow-up for a minimum 6-month-period after serotonin receptor inhibitor treatments were initiated., Results: We found that miR-26a-5p ( P < .001), miR-21-3p ( P < .001), miR-219a-1-3p ( P = .016), miR-106b-5p ( P = .039), miR-6740-5p ( P = .020), miR-320a ( P = .001), miR-22-3p, and miR-16b-5p ( P = .010) expression levels were statistically higher in obsessive-compulsive disorder patients than healthy controls; miR-135a-5p ( P < .001) and miR-129-6b-5p ( P < .001) expression levels were statistically lower. Also, it was determined that increased miR-106b-5p levels were associated with treatment-resistance ( P = .020) and there was a negative correlation between miR-374b-3p and disease severity ( P = .042)., Conclusion: In obsessive-compulsive disorder, there may be a potential value in the relationship between various miRNA expression levels and treatment resistance and disease severity, and future studies may be beneficial., (2022 authors.)