Background Special AT‐rich binding protein‐1 (SATB1) reprograms chromatin organization and transcription profiles to promote tumour growth and metastasis. Aims This study aimed to confirm the effects of SATB1 on the growth and metastasis of liver cancer and its specific regulation mechanism. Methods SATB1 expression was evaluated in human hepatoma tissue, adjacent noncancerous tissue and seven kinds of liver cancer cell lines. Cell cycle, cell proliferation, apoptosis and eptithelial‐mesenchymal transition (EMT) was investigated after enhanced or silenced expression of SATB1. The regulatory action of SATB1 on the expression of genes that are known to regulate cell cycle progression, apoptosis and EMT and the specific apoptotic pathway on which it acts were further analysed. Nude mice that received subcutaneous implantation were used to study the effects of SATB1 on tumour growth in vivo. Results Our data show that the high expression of SATB1 was observed in the human hepatocellular carcinoma tissue (26/45) and liver cancer cell lines with high metastatic potential. SATB1 upregulated CDK4 and downregulated p16 INK 4A to promote cell cycle progression and cell proliferation and prevented apoptosis by inhibiting the FADD–caspase‐8–caspase‐3 death receptor‐mediated apoptosis pathway. SATB1 also induced EMT concomitant with increased expression of Snail1, Slug, Twist and vimentin and decreased expression of E‐cadherin, tight junction protein ZO‐1 and desmoplakin. SATB1 promoted the growth of tumour in vivo. Conclusion These data suggest that the SATB1 gene may play an important role in the development and progression of liver cancer by regulation of genes related to cell cycle progression, apoptosis and EMT.