Osteoarthritis is a type of arthritis that is caused by breakdown of cartilage, with eventual loss of the cartilage of the joints. The ability of self-repair in damaged cartilage tissue is limited; the aim of this work is to fabricate and characterize an oxidized hyaluronic acid/resveratrol (Oxi-HA/Res) hydrogel for future applications in cartilage tissue engineering. Under physiological conditions, the Oxi-HA/Res hydrogel was prepared by chemical crosslinking of Oxi-HA with resveratrol solution and characterized by Fourier transform infrared spectrometry assay; the biocompatibility and gene expression of chondrocytes within the Oxi-HA-Res hydrogel then analyzed. The cell viability and cytotoxicity assays showed that the Oxi-HA/Res hydrogel has good biocompatibility. Oxi-HA/Res hydrogel can upregulate expression of type II collagen, aggrecan, and Sox-9 genes; while down-regulating IL-1β, MMP-1, MMP-3, MMP13 gene expression. It can also reduce LPS-induced inflammation and chondrocyte damage. The results of this study showed that the Oxi-HA/Res hydrogel is biocompatible with chondrocytes, allows for extracellular matrix synthesis, and also reduce LPS-induced inflammation and damage. These results suggest that Oxi-HA/Res hydrogel may be a potential suitable cell carrier for chondrocyte cells in the treatment of cartilage defect. However, further in vivo study is mandatory for future possible clinical applications. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 3457–3466, 2013.