BACKGROUND Osteoarthritis (OA) affects about 40% of people older than 40 years of age, and the mechanism is not well understood. Long non-coding RNA (lncRNA) CAIF is a recently identified critical player in myocardial infarction, while its role in other human diseases is unclear. The present study aimed to investigate the role of CAIF in OA. MATERIAL AND METHODS Levels of CAIF in synovial fluid of OA patients (n=60) and healthy controls (n=60) were measuring by performing quantitative real-time polymerase chain reaction (qRT-PCR). MiR-1246 and interleukin (IL)-6 levels in synovial fluid were measured by performing qRT-PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Cell apoptosis analysis was performed after CHON-001 cells were treated with 500 mg/mL lipopolysaccharide (LPS) for 24 hours. RESULTS We found that CAIF in synovial fluid was downregulated in OA patients and inversely correlated with miR-1246 and IL-6. Downregulated CAIF distinguished OA patients from healthy controls. In cells of chondrogenic cell line CHON-001, CAIF overexpression mediated the inhibited expression of miR-1246 and secretion of IL-6, while miR-1246 overexpression reduced the effects of CAIF overexpression on IL-6 secretion. In addition, CAIF overexpression inhibited the apoptosis of CHON-001 cells under LPS treatment, while miR-1246 overexpression attenuated the effects of CAIF overexpression. CONCLUSIONS Therefore, CAIF may downregulate miR-1246 to improve OA.