Here, we demonstrated that there is an important regulatory axis present in certain situations, such as tumor initiation and metastasis, involving high levels of Twist1 binding to miR-26b-5p to downregulate miR-26b-5p expression, resulting in less SMAD1 suppression, inactivation of BMP4/Smad1 signaling, and the promotion of EMT, ultimately contributing to tumor progression in HCC. This evidence concerns the gene SMAD1 and neoplasm.