Objective: To explore the relationship between expressions of cell adhesion molecules CD44 v6 and E-cadherin (E-cad) and lymphatic metastasis in non-small cell lung cancer (NSCLC). Materials and Methods: Eightyseven tissue samples obtained from patients with primary NSCLC were collected in our hospital from Dec., 2007 to Dec., 2012, and the expressions of CD44 v6 and E-cad gene proteins in these samples were detected by immunohistochemical method. Results: In the tissue without lymphatic metastasis, the positive expression rate of CD44 v6 was significantly lower, whereas the normal expression rate of E-cad was notably higher than that with lymphatic metastasis (55.6% vs. 78.4%, 47.2% vs. 21.6%), and both differences had statistical significance (P<0.05). Besides, CD44 v6 and E-cad expressions had a significant correlation in the NSCLC tissue with lymphatic metastasis (P<0.05). Conclusions: The positive expression of CD44 v6 and abnormal expression of E-cad may play a very important role in promoting lymphatic metastasis of NSCLC, with synergistic effect. Hence, detection of CD44 v6 and E-cad expressions is conductive to judging the lymphatic metastasis in NSCLC.