This study aims to research the expression of spleen tyrosine kinase (Syk) in non-small cell lung cancer (NSCLC) and the relationship between Syk and clinico-pathologic factors and p53. Immunohistochemistry was applied to detect the expression of Syk and p53 protein in 39 cases of NSCLC (23 cases of lung squamous cell can-cer, 16 cases of lung adenocarcinoma) and tumor-sur-rounding normal lung tissues. The positive rate of Syk was 46.15% (18/39) and 100% (39/39) in NSCLC and tumor-surrounding normal lung tissues, respectively. The expres-sion level of Syk in NSCLC was significantly lower than that in tumor-surrounding normal lung tissues (P = 0.000). The Syk expression was positively correlated with the p53 expression in NSCLC specimens (P = 0.025). There was no significant association between Syk expression and lymph node metastasis, differentiation degree, tumor size and tumor node metastasis (TNM). The present study demonstrated that Syk was aberrantly expressed in the NSCLC and might have a significant impact on tumor growth and progression.