Objective This study is aimed to get the gene expression signatures of calmodulin by mining data from Oncomine database as well as proving them with our samples. Methods Differential calmudulin mRNA expression levels in the head and neck squamous cell carcinoma(HNSCC) were got from Oncomine database, and the expression of calmodulin on mRNA and protein level of the clinical samples and oral carcinoma cell lines was analyzed by real-time polymerase chain reaction and Western Blotting, respectively. Results The results indicated that in most of databases of HNSCC samples compared to adjacent non-tumor(or normal) tissue presented a significant increase in calmodulin mRNA level, but only a few not. The results from our experiments show that the expression of calmodulin on mRNA and protein level of normal tissue is more higher than that of tumor tissue. Conclusion We can get the information about the expression of calmodulin mRNA level on HNSCC quickly and exactly by combining data-mining from Oncomine database with our verified experiment. This can make a ground for the developmental research about calmodulin.