Objective: Serum AXL expression and clinical significance in patients with knee osteoarthritis (KOA). Methods: 183 patients with knee osteoarthritis were selected and divided based on the Kellgren-Lawrence (KL) score into KL 0 subgroups (n = 42), KL I-II subgroups (n = 90), and KL III-IV subgroups (n = 51). Healthy volunteers (n= 170) in our hospital were selected as the control group. AXL level in serum was detected by enzyme-linked immunosorbent assay (ELISA). The correlation between serum AXL with severity and clinical indicators of osteoarthritis was analyzed. Results: The level of serum AXL was significantly higher in the osteoarthritis group than that in the control group (P<0.05). In the osteoarthritis patients, serum AXL level was increased with the increase of KL score. Serum AXL level was positively correlated with age, body mass index (BMI), erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP), cartilage oligomeric protein (COMP), matrix metalloproteinase-13 (MMP-13), and transforming growth factor-β1 (TGF-β1) levels. The cut-off value for serum AXL was determined as 33.375 ng/mL by receiver operating curve (ROC) analysis. Conclusion: The level of serum AXL in patients with osteoarthritis is abnormally high, which is closely related to the severity of osteoarthritis.