Objectives: Dual immunoglobulin domain containing cell adhesion molecule (DICAM) is a type I transmembrane protein, which presents in various cells including renal proximal tubular cells. The effects of DICAM against tubular oxidative stress are unclear. We evaluated the expression and protective role of DICAM in renal tubular cell injury. Methods: HK-2 cells were incubated and treated with lipopolysaccharide (LPS; 30 μg/mL) or hydrogen peroxide (H2O2; 100 μM) for 2, 4, and 24 hours. DICAM expression, inflammatory markers, and apoptosis assay were evaluated. Small interfering RNA of DICAM was used to investigate the effect of the gene silencing of DICAM. Results: Protein expression level of DICAM increased significantly after treatment with LPS or H2O2 in HK-2 cells. DICAM showed an earlier increase (2 to 4 hours after treatment) than neutrophil gelatinase-associated lipocalin (NGAL; 24 hours after treatment) in response to oxidative stress. The gene silencing of DICAM increased protein expression of inflammation-related markers such as integrin β1 and integrin β3 in both LPS and H2O2-induced HK-2 cell injury. DICAM gene knockdown decreased the Bcl-2/Bax ratio in both LPS and H2O2 injury, which indicates an increase in apoptosis. Conclusions: DICAM can be an early diagnostic marker for detecting tubular damage in kidney injury. DICAM may protect renal tubular injury via anti-inflammatory and anti-apoptotic action.