Hepatocellular carcinoma (HCC) is worldwide accepted most common malignancies, as well as the second major cause of death among Chinese with cancer. There is an increasing evidence that could prove the potential effect of long non-coding RNAs (lncRNAs) to the biological performance of HCC. In present study, with high expression level in The Cancer Genome Atlas (TCGA) HCC samples, lncRNA MFI2 Antisense RNA 1 (MFI2-AS1) was closely related to poor prognosis and advanced stage among patients with HCC. In addition, up-regulation of MFI2-AS1 was further comfirmed in HCC tissues and HCC cell line. Ectopic expression of MFI2-AS1 stimulated the proliferation and metastasis of HCC cells, but knockdown MFI2-AS1 suppressed HCC cell proliferation and metastasis, indicating that MFI2-AS1 exerted oncogenic functions in the tumorigenesis of HCC. Simultaneously, compared with the negative control group, xenograft tumors in MFI2-AS1 group were characterized with poor growth, smaller volumes and less liver metastases. The post-transcriptional regulation of FOXM1 by MFI2-AS1 occured mechanistically, playing a role of competing with endogenous RNA (ceRNA) in HCC to sponge miR-134. Over-expression of MFI2-AS1 increased FOXM1 expression both at mRNA and protein level, whereas it was reducd by miR-134. Meanwhile, knockdown of miR-134 abolished the repression of shMFI2-AS1 on FOXM1 expression. Furthermore, we demonstrated that miR-134 reverses the impact of MFI2-AS1 on HCC proliferation and metastasis through regulation on FOXM1. Collectively, we determined that MFI2-AS1 crucially acted in HCC progression via functioning as miR-134 sponge to upregulating FOXM1 expression, and was conducive to the promotion of better understanding the direct diagnostics and iatreusiology of lncRNA in HCC.