This study was aimed to investigate the anti-tumor, anti-metastasis and immunomodulatory effects of Yifei Tongluo (YFTL), a Chinese herbal formula, in Lewis lung carcinoma mice and to explore the underlying mechanisms. LLC cells were inoculated subcutaneously in C57BL/6 mice to establish the Lewis lung carcinoma model. We observed that YFTL effectively inhibited tumor growth and prolonged the overall survival of tumor-bearing mice. Additionally, YFTL treatment resulted in a significantly decreased number of surface lung metastatic lesions compared with the model control group. Meanwhile, TUNEL staining confirmed that the tumors from YFTL-treated mice exhibited a markedly higher apoptotic index. The results suggest that Akt and mitogen-activated protein kinase (MAPKs) pathways may be involved in YFTL-induced apoptosis. The results show that YFTL also inhibited the vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMP)-2, MMP-9, N-cadherin, and Vimentin expression, but increased E-cadherin expression. Mechanistic studies indicated that YFTL could suppress the angiogenesis and the epithelial-mesenchymal transition (EMT) of the tumor through Akt/ERK1/2 and TGFβ1/Smad2 pathways. In addition, YFTL also showed immunomodulatory activities in improving the immunosuppressive state of tumor-bearing mice. Therefore, our findings could support the development of YFTL as a potential antineoplastic agent and a potentially useful anti-metastatic agent for lung carcinoma therapy.