In the present study, we used in vitro angiogenesis-related experiments, an in vivo subcutaneous tumour model and an in vivo liver metastasis model to demonstrate that bufalin can inhibit TME-mediated STAT3 activation in endothelial cells to reduce angiogenesis, identifying a new mechanism of action of bufalin in the treatment of CRC. This evidence concerns the gene STAT3 and colorectal carcinoma.