Purpose: To investigate whether miR-449a can regulate the biological functions of hepatocellular carcinoma (HCC) cells by targeting special AT-rich sequence binding protein 1 (SATB1). Methods: qRT-PCR and western blot were carried out to detect the expression of miR-449a and SATB1 in normal human hepatocyte cell line HL-7702 and in HCC cells SMMC7721, Hep3B, HepG2, and Bel-7402. miR-449a-mimics, miR-negative control (miR-NC), specifically inhibited SATB1 RNA (si-SATB1), specifically overexpressed SATB1 RNA (shSATB1), and negative control RNA (Si-NC) were transfected into the Hep3B and Bel-7402 cells. MTT assay, Transwell assay and flow cytometry were conducted to detect cell proliferation, invasion, and apoptosis. Dual luciferase reporter assay was performed to determine the relationship between miR-449a and SATB1. Results: miR-449a was highly but SATB1 was poorly expressed in HCC cells. According to the cell experiments, the up-regulation of miR-449a expression could inhibit the proliferation and invasion of HCC cells, promote their apoptosis, and significantly reduce SATB1 expression. The inhibition of SATB1 expression could inhibit the proliferation and invasion and promote apoptosis. The dual luciferase reporter assay confirmed that there was a targeted regulatory relationship between miR-449a and SATB. Conclusion: miR-449a can inhibit the proliferation and invasion of HCC cells and promote their apoptosis through the targeted regulation of SATB1, so it is expected to become a potential therapeutic target for this disease in clinical practice.