Osteoarthritis (OA) is characterized by synovial cartilage degeneration and is the leading cause of disability and pain worldwide. This study sought to investigate the expression of integrin beta-2 (ITGB2) in synovial fluid of OA patients and its clinical significance. A total of 110 OA patients were enrolled, who were classified into grade I (N = 35), II (N = 42), and III (N = 33) according to the Kellgren-Lawrence classification, with 110 healthy subjects as controls, and their clinical data were compared. ITGB2 level was detected by RT-qPCR. The receiver operating characteristic curve was used to analyze the predictive value of ITGB2 on OA occurrence. The correlation between ITGB2 and bone metabolism indexes procollagen type I N-terminal peptide (PINP), bone glaprotein (BGP), bone alkaline phosphatase (BALP), and β-collagen I telopeptide (β-CTX) was analyzed by the Pearson method. Logistic regression model was performed to analyze the influencing factors of OA. The content of red blood cells, white blood cells, PINP, BGP, and BALP was lowered in OA patients, while β-CTX was elevated. ITGB2 was highly-expressed in OA patients, negatively-correlated with PINP, BGP, and BALP, but positively-correlated with β-CTX. ITGB2 level increased with the elevation of OA grade. The ITGB2 level >1.375 had certain diagnostic values for OA. ITGB2 level is related to OA severity and may be a biomarker for OA classification. ITGB2 was an independent risk factor for OA. High expression of ITGB2 in synovial fluid can assist OA diagnosis and may be a biomarker for OA grade.