Purpose: This study was to find efficacy of integrin alpha2 (${alpha}_2$) and epidermal growth factor receptor (EGFR) as tumor marker of oral squamous cell carcinoma (SCC) and clarify the selective cell death effect of anti-integrin ${alpha}_2$ and anti-EGFR on SCC cells, additionally testify conjugated gold nanoparticles (GNP) with air plasma for selective cell death of oral SCC. Methods: Expression of integrin ${alpha}_2$, EGFR on human SCC cells (SCC25) were examined by western blot. SCC25 cells were treated with anti-integrin ${alpha}_2$, anti-EGFR and analysed by Hemacolor staining, immunoflorescence staining, FACS flow cytometry. Conjugated GNP with integrin ${alpha}_2$, EGFR antibody were treated by air plasma on SCC cells. Results: Integrin ${alpha}_2$ and EGFR were over-expressed on SCC25 cells than normal lung WI-38 cells. The cell viability rate of SCC25 cells treated with anti-integrin ${alpha}_2$, anti-EGFR was lower than WI-38 cells. The concentration changes of nucleus, releasing cytochrome c and apoptosis inducing factor (AIF) from mitochondria to cytosol were observed. The changes of proteins related with apoptosis were observed. Increase of bax, bcl-xL, activation of caspase-3, -7, -9, and fragmentation of PARP, DFF45 and decrease of lamin A/C in SCC25 cells were observed. In FACS, increase of sub-$G_1$ and S phase was observed. Cell cycle related proteins, Such as cyclin D1, cyclin dependent kinase (CDK) 4, cyclin A, cyclin E, CDK 2, p27 were decreased. After SCC25 cells treated with conjugatged GNP-Integrin ${alpha}_2$, GNP-EGFR, additionally air plasma, the cell death rate was significantly increased. Conclusion: Integrin ${alpha}_2$, EGFR were over-expressed in oral SCC cells. Anti-integrin ${alpha}_2$, anti-EGFR in SCC25 cells induced apoptosis selectively. When GNP-anti integrin ${alpha}_2$, GNP-anti EGFR were treated with air plasma on SCC25 cells, cancer cells were died more selectively. GNP-anti integrin ${alpha}_2$, GNP-anti EGFR with air plasma could be treatment choice of oral SCC.