Objective To explore the expression of vascular endothelial growth factor receptor 3 (VEGFR3) and its significance in lung adenocarcinoma and to examine the effect of VEGFR3 knockdown on the biological behaviors of A549 cells. Methods Immunohistochemistry was used to detect the expression of VEGFR3 in 78 pieces of lung adenocarcinoma tissue and 35 of paracancerous tissue. Relationships between VEGFR3 and clinicopathological indices were also analyzed. Correlations between lung adenocarcinoma patient survival and the expression of vascular endothelial growth factor-C (VEGF-C) or VEGFR3 were analyzed using the TCGA database. VEGFR3 expression was knocked down in A549 cells using RNA interference, and cell proliferation was assessed using a CCK-8 assay. Cell migration and invasion were detected using TranswellTM assays. The effect of siRNA-mediated knockdown of EGFR3 in A549 cells on AKT pathway activity was assessed by Western blot analysis. Results Expression of VEGFR3 was significantly higher in the lung adenocarcinoma tissue than in the adjacent tissue, and positively correlated with TNM stage and lymph node metastasis. The survival rate of patients with high VEGFR3 expression was significantly lower than that of patients with low VEGFR3 expression. Exogenous VEGF-C promoted the expression of VEGFR3, and activated the AKT signaling pathway. Silencing of VEGFR3 inhibited the proliferation, migration, and invasiveness of A549 cells, and reduced the activation of the AKT signaling pathway by VEGF-C. Conclusion High expression of VEGFR3 in the lung adenocarcinoma tissue is positively correlated with poor prognosis. Silencing VEGFR3 can block AKT pathway activity and inhibit the proliferation, migration, and invasion of A549 cells.