Abstract: Objective To explore the relationship between the expression of miRNA-27 a and miRNA-146 a in serum and the pathogenesis of osteoarthritis(OA). Methods A total of 75 patients with OA in our hospital were selected from May 2017 to December 2018, meanwhile 63 non-OA patients and 44 healthy people who were treated at the same time were selected as the study objects according to gender and age as matching factors. The expression of miRNA-27 a and miRNA-146 a in synovial tissue and plasma were detected by RT-qPCR. The factors influencing the expression of miRNA and the diagnostic value of OA patients were observed. Results The expression of miRNA-27 a and miRNA-146 a in synovial tissue and plasma of OA patients was significantly higher than that of other patients(P<0.05), with a better correlation(r=0.425; r=0.622, all P<0.05). The relative expression of miRNAs in synovial tissue and plasma was significantly increased in OA patients with aged> 65 years, female, advanced and obese(P<0.05). The diagnostic accuracy, sensitivity, specificity and Kappa values of plasma miRNA-27 a were 80.8%, 90.7%, 73.8% and 0.619, respectively. The diagnostic results of plasma miRNA-146 a were 76.9%, 86.7%, 70.1% and 0.544, respectively. The tandem diagnostic results were 90.6%, 86.3%, 93.5%, and 0.803, respectively. Conclusion miRNA-27 a and miRNA-146 a are highly expressed in OA patients, which has better diagnostic value. The expression trend in plasma and synovium is the same. Women, old age, advanced OA and obesity may be responsible for the elevation of both miRNAs.