Background: Osteoarthritis (OA), the most prevalent disease of articulating joints, is a complex multifactorial disease caused by genetic, mechanical, and environmental factors. In this research, we evaluated miRNA expression in OA. Methods: Forty tissue samples from 29 patients undergoing joint replacement for OA were evaluated. Tissue from two control patients undergoing hip replacement not related to OA was used as a control. Total RNA (containing miRNA species) from cartilage was isolated using a mirVana miRNA Isolation Kit. Expression of 19 miRNAs was assessed by real-time quantitative polymerase chain reaction. Results: Expression of four miRNAs, miR-138-5p, miR-146a-5p, miR-335-5p, and miR-9-5p, was significantly upregulated in OA tissues (patients vs. control group). Conclusions: These findings may contribute to disease prevention and the development of therapeutic targets for OA.