Abstract: Objective To analyze the correlation between the expression of PTEN and LKB1 in non-small cell lung cancer (NSCLC). Methods Paraffin blocks of 74 cases of NSCLC patients were collected, and the expression of LKB1 and PTEN were detected by immunohistochemistry. The clinical related index and the correlation with the expression of PTEN and LKB1 were analyzed to explore the expression clinical significance of them. Results The PTEN and LKB1 expression positive rate were 47.3% and 70.3%, respectively. LKB1 expression negative samples were mostly associated with PTEN negative expression. Statistical analysis showed that LKB1 was positively correlated with PTEN expression ( r=0.287, P=0.017). The expression of PTEN and LKB1 in NSCLC had no relationship with gender, age and pathology type ( P>0.05). The expression of PTEN is closely associated with lymph node metastasis (LNM, P=0.017), invasion ( P=0.008) and clinical stage ( P=0.019). And lack expression of LKB1 was closely associated with tissue invasion ( P=0.043) and clinical stage ( P=0.003). Patients with PTEN and LKB1 positive showed more LNM and/or invasion than those with them negative. Conclusion The expression of PTEN and LKB1 may be related to the occurrence and progression of NSCLC, and may have a synergistic effect, and it can be used as a judgment of the prognosis of NSCLC.