In our past study, we confirmed the highest Loss of heterozygosity frequency in 4q25 (D4S2623), and we observed gene Caspase-6 in the proximity to D4S2623, which has a relevant function during apoptosis and therefore can also work like TSG. So we examined Caspase-6 mRNA expression level. Reverse-transcription-PCR analysis demonstrated decreased expression in 40% and equal expression in 30% of Caspase-6 mRNA of primary tumors as compared with the matched normal samples. We also examined Caspase-6 cDNA sequencing for mutations. But no mutation was detected. These findings suggested the possibility of Caspase-6 gene to function as a tumor suppressor gene in a subset of oral SCC.