To explore whether lncRNA deleted in lymphocytic leukemia 2 (DLEU2) could accelerate the migratory, invasive and proliferative abilities, thus influencing the progression of HCC. DLEU2 level in HCC tissues and adjacent normal tissues was firstly determined. Its level in HCC tissues with different tumor sizes (≤ 5 cm or > 5 cm), different tumor stages (stage I-II or III-IV) and either with vascular invasion or not was determined. Potential influences of DLEU2 on proliferative, migratory and invasive abilities of SMMC7721 and HCLM3 cells were assessed. The interaction between DLUE2 and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) was evaluated by RNA Binding Protein Immunoprecipitation (RIP) assay. Finally, the effect of DLEU2/EZH2 regulatory loop on proliferative ability of HCC cells was detected. DLEU2 was upregulated in HCC tissues, especially in those larger than 5 cm in tumor size, accompanied with vascular invasion and in worse tumor stage. Knockdown of DLEU2 attenuated proliferative, migratory and invasive abilities of SMMC7721 and HCLM3 cells. RIP assay proved that DLEU2 could interact with EZH2. Knockdown of EZH2 attenuated the inhibited proliferation in HCC cells with DLEU2 knockdown. DLEU2 accelerates the proliferative, migratory and invasive abilities of HCC cells via binding to EZH2, thus aggravating the progression of HCC.