Abstract UV r-1 UV-resistant cells were established from UV-sensitive human RSa cells. We looked for genes expressed differentially between UV r-1 and RSa cells using PCR-based mRNA differential display to elucidate the molecular mechanisms underlying UV resistance. The transcription levels of syndecan-1 mRNA were increased in UV r-1 cells compared with those of RSa cells. Syndecan-1 is a transmembrane heparan sulfate proteoglycan and associates with cell adhesion and the cytoskeleton. Flow cytometric analysis using anti-syndecan-1 monoclonal antibody revealed that syndecan-1 was more abundant in UV r-1 cells than in RSa cells. The MTT method revealed that UV r-1 cells treated with the antibody showed higher sensitivity to UV cell killing than mock-treated cells. Studies using antisense oligonucleotides for syndecan-1 showed that antisense-treated UV r-1 cells became sensitive to UV cell killing. Thus, syndecan-1 might be involved in UV resistance in UV r-1 cells.