Abstract:[Objective] To explore the clinical efficacy and safety of intra-articular injection of umbilical cord blood mononuclear cells (UCB-MNCs) for treatment of knee osteoarthritis (KOA) . [Methods] From February 2021 to September 2022, 30 patients received intraven- tricular injection of 2×108 (3 ml) UCB-MNCs twice with one month apart for early- and mid-stage KOA. The clinical and imaging data were evaluated. [Results] All the patients had the injection completed successfully, with the main adverse reactions of joint swelling and pain with- in a few days after injection, whereas which not affected functional activities of the joint. There were no significant changes in blood routine, erythrocyte sedimentation, C-reactive protein, liver function and kidney function before and after treatment. As time went during the followup lasted for 6 months, the VAS scores for pain and swelling, as well as WOMAC pain, stiffness, function, and overall scores significantly de- creased (P<0.05) , while all KOOS subscores significantly increased (P<0.05) . Radiographically, the Kellgren-Lawrence grades in the medi- al, lateral and patellofemoral compartments remained unchanged (P>0.05) , the MRI Osteoarthritis Knee Score (MOAKS) of the medial com- partment was not changed either (P>0.05) , while the MOAKS scores of the lateral and patellofemoral compartments significantly decreased 3 months after treatment compared with those before treatment (P<0.05) . [Conclusion] Intra-articular injection of UCB-MNCs for KOA does effectively relieve pain and improve function in this trial.