INTRODUCTION: The pro-inflammatory cytokine interferon-gamma (IFN-纬) is reported to be an agent that boosts the immune modulation of mesenchymal stem cells (MSCs). However, the effects of IFN-纬 on the chondrogenic potential of treated MSCs have not been evaluated in depth. This study aimed to evaluate the effects of IFN-纬 on the immune modulation and chondrogenic potential of human umbilical cord-derived MSCs (hUC-MSCs). METHODS: UC-MSCs were isolated and expanded following published protocols. They were characterized as MSCs before their use in further experiments. The UC-MSCs were treated with IFN-纬 at 10聽ng/mL for 48聽h. Changes in phenotype were investigated based on changes in MSC markers, immunomodulatory genes (TGF-尾, IL-4, and IDO) for immune modulation, and cartilage-related genes during the induction of differentiation (Col1a2, Col2a1, Sox9, Runx2, and Acan) for chondrogenic potential. RESULTS: IFN-纬-treated UC-MSCs maintained MSC markers and exhibited decreased expression of transcriptional regulatory factors in chondrogenesis (Sox9 and Runx2) and the extracellular matrix-specific genes Col1a2 and Acan but not Col2a1 compared to non-treated cells (p聽<聽0.05). Furthermore, the immunomodulatory capability of IFN-纬-treated UC-MSCs was clearly revealed through their increased expression of IDO and IL-4 and decreased expression of TGF-尾 compared to non-treated cells (p聽<聽0.05). CONCLUSION: This study demonstrated that UC-MSCs treated with IFN-纬 at 10聽ng/mL had reduced expression of chondrocyte-specific genes; however, they maintained multi-lineage differentiation and exhibited immunomodulatory properties.