The Mechanism of laser therapy and also its safety are 2 important features of the application of different types of lasers in medicine. This study aims to investigate the critically affected genes after the treatment of squamous cell carcinoma patients. The gene expression profiles of 4 squamous cell carcinoma patients that were treated via chemoradiotherapy (CRT) plus the laser and 3 similar patients without laser exposure from Gene Expression Omnibus (GEO) were downloaded and were screened to find critical genes via network analysis. The STRING database, Cytoscape software, and the Clue GO plug-in of Cytoscape software were used. The genes HSX70 and NCC27 were determined as neighbors and HSPA1B, CLIC1, RAB13, PPIF, and LCE3D as hub genes. The over-expression of LCE3D was interpreted as the side effect of laser therapy. Apoptosis and the cell cycle were the dominant biological processes regulated by the HSP molecules in the laser-treated patients. The laser affected the main biological processes and simultaneously issued side effects.