To observe the mechanism of interaction between SEMA7A and its receptor in the migration of A549 cells. Methods The effect of interaction between SEMA7A and plexin C1 in A549 cells migration and migration related signaling pathway were detected using SEMA7A and plexin C1 small interfering RNA. Results The expression of SEMA7A and plexin C1 were significantly increased in A549 cells compared with normal alveolar epithelial cells. SEMA7A increased the expression of tumor migration related protein CCR-7, MMP-2 and MMP-9. However, the expression of CCR-7, MMP-2 and MMP-9 decreased when SEMA7A and plexin C1 were silenced. Conclusion The interaction between SEMA7A and plexin C1 promoted the migration of A549 cells.