Objective To investigate the differently expressed Homeobox genes between lingual squmaous cell carcinoma and normal mucosa. Methods Seven paired specimens including lingual squmaous cell carcinoma and its surrounding normal tissue were obtained from 7 patients. Customized Oligo microarray which contains numerous probes of 232 human Homeobox genes was used to analyse the results. All datas were scanned by Agilent scanner and differentiately expressed genes were sorted out. Results Homeobox gene NANOG was found up- regulated in 5 samples. PHTF2 was found down- regulated in 7 samples, and CRX, PITX1, OTEX was found down- regulated in 5 samples. Conclusion As the key gene to cellular proliferation and differentiation, Homeobox genes is closely releverant to the oncogenesis of lingual squmaous cell carcinoma.