Hepatocellular carcinoma (HCC) is one of the most common malignancies. Long non-coding RNAs (lncRNAs) are involved in HCC. This study aimed to explore the effects of lncRNA MALAT1 on HCC development. MALAT1, ZEB1, and miR-143-3p in HCC tissues was detected by qRT-PCR. Effect of MALAT1 on the proliferation and metastasis of HCC cells was estimated by cell-counting, wound-healing, and transwell assays. Luciferase reporter assays were used to explore miR-143-3p's target, ZEB1. QRT-PCR and Western blot were employed to determine the effects of MALAT1 or/and miR-143-3p on ZEB1 expression. MALAT1 was upregulated in HCC tissues. ZEB1 was a target of miR-143-3p. miR-143-3p binds with MALAT1, and was regulated by MALAT1. The regulation of MALAT1 on ZEB1 was mediated by miR-143-3p. Transfection with siR-MALAT1 significantly inhibited cell proliferation and invasion, while knockdown of miR-181a partially reversed these effects. Our findings suggest that MALAT1 may regulate ZEB1 expression by sponging miR-143-3p and promotes hepatocellular carcinoma progression. J. Cell. Biochem. 118: 4836-4843, 2017. © 2017 Wiley Periodicals, Inc.