Oral cancer overexpressed 1 (ORAOV1) is a crucial oncogene in oral squamous cell carcinoma (OSCC). In this study, we have identified a novel splice variant of ORAOV1, designated as ORAOV1-A. To study the potential role of ORAOV1-A in OSCC, we tested its expression in 7 OSCC cell lines, as well as in 19 normal oral tissue samples and 47 OSCC tissue samples. The expression of ORAOV1-A was detectable in 6 out of 7 OSCC cell lines tested. In OSCC tissue samples, the expression frequency of ORAOV1-A (51.1%) was much higher than that in normal samples (10.5%). Notably, an inverse correlation was found between the expression frequency of ORAOV1-A and the degree of differentiation in OSCC (P = 0.0017). In conclusion, our results suggested that ORAOV1-A may play a functional role in the tumorigenesis of OSCC, and ORAOV1-A expression may serve as an adjunctive prognostic indicator for persons with OSCC.