Osteoarthritis (OA) is a significant joint disease that can affect the health of individuals in many sectors. Although OA is primarily known as a joint disease in the field of health, it can also cause damage to organs such as the liver due to the systemic inflammatory reactions (SIRS) it triggers. Boric acid (BA), which has been the subject of many studies and has been shown to have anti-inflammatory, anti-apoptotic, antimicrobial, and anticancer properties, is widely used in various areas of the healthcare sector. In this study conducted for this purpose, the protective effect of BA against liver damage caused by OA was investigated. A total of 28 rats were divided into four groups, each consisting of 7 rats. Except for the control group, all animals were induced with monosodium iodoacetate (MIA) to develop OA, and then rats were administered doses of BA ranging 4 and 10 mg/kg for 21 days. In histopathological examinations, severe hepatitis and degenerative changes were observed in the liver tissue of the OA-induced group, while it was found that BA application reduced these damages dose-dependently. Similarly, in immunohistochemical analyses, it was observed that OA induction significantly increased the expression levels of TNF-α, IL-1β, NOS, and MMP in the liver, but in the groups treated with BA, this expression level significantly decreased depending on the dose. In this study, it was observed that BA exhibited anti-inflammatory properties and had a protective effect on liver tissue against SIRS caused by OA.