The objectives of this study was to explore the growth pattern of the oral squamous cell carcinoma when overexpressed COX was inhibited, explore the pathway that COX inhibitors suppressed the proliferation of cancer cells, and then hereafter investigate the potential of COX as chemopreventive target for oral squamous cell carcinoma. For confirming the COX-dependent effect and mechanisms on growth of the oral cancer cells, we treated the nonselective NSAID, Mefenamic acid and COX-2 selective inhibitor, Celecoxib in HN4 cell line. And then the cell line was evaluated with MTT assay and growth curve, the production of PGE2, total RNA extraction and RT-PCR analysis, and TEM The results were obtained as follows: 1. After administration of medication, in the result of MTT assay, Celecoxib inoculated group inhibit the cell growth rather than Mefenamic acid inoculated group. 2. The growth curve of cell line showed as time passes by there was a dramatic cell growth in the control group, and gradual growth inhibition was found in medication inoculated group and, in Celecoxib inoculated group there was more inhibition of cell growth. 3. After the administration of medication, Celecoxib tend to inhibit the synthesis of PGE2 more than Mefenamic acid. Mefenamic acid inhibit the synthesis of PGE2 more as the concentration gets high, but Celecoxib inhibited the synthesis of PGE2 even in low concentration. 4. After the administration of medication, the revelation of COX mRNA in cell line, there was a 50% decrease in COX-1, 60% decrease in COX-2 as in $50{mu}M$ Mefenamic acid, and in Celecoxib $50{mu}M$ there was not much difference in COX-1 and 90% decrease in COX-2 was found. 5. HN4 cell line showed broken nucleus and tangled cytoskeleton bundles in cytoplasm which meant apoptotic features after the treatment of Celecoxib in TEM view. Depending on the above results, we estimate that the inhibition of the expression of COX-2 cause the growth suppression of the oral squamous cell carcinoma, and it get achieved through pathway of reduced PGE2 production and increased apoptosis. In addition to, because COX-2 selective inhibitor specifically act to COX-2, it is considered that COX-2 selective inhibitor has the adequate potential as chemopreventive agent for oral squamous cell carcinoma.