Oral lichen planus (OLP) is a chronic inflammatory mucosal disease that cell-mediated immunological mechanisms are involved in pathogenesis. The objective of this study was to investigate the expression of CD44 isoforms including CD44s, CD44v5, and CD44v6 in biopsy specimens and saliva from OLP patients. Thirty-one OLP patients and 30 healthy subjects were enrolled in this study. Immunohistochemical methods were used to detect the expression of CD44 isoforms in oral epithelia, and enzyme-linked immunosorbent assay (ELISA) was performed to measure levels of salivary CD44 isoforms. Our results demonstrated that expression of CD44v6 in oral epithelia from OLP patients was significantly decreased in comparison to controls (p = 0.021). Levels of salivary CD44s and CD44v5 from OLP patients were significantly higher than those from controls (p = 0.007 and p = 0.002, respectively). In summary, our findings provided additional evidence that the pathological stress, such as chronic inflammation, altered the expression of CD44 isoforms in oral epithelia and saliva of OLP patients.