JMJD2A accelerates malignant progression of liver cancer cells in vitro and in vivo. Mechanistically, JMJD2A promoted the expression and mature of miR372 epigenetically. Thereby, miR372 blocks the editing of 13th exon-introns-14th exon and forms a novel transcript (JMJD2AΔ) of JMJD2A. JMJD2A inhibited P21(WAF1/Cip1) expression by decreasing H3K9me3 dependent on JMJD2AΔ. Moreover, JMJD2A could enhance Pim1 transcription by suppressing P21(WAF1/Cip1). Furthermore, through increasing Pim1, JMJD2A could facilitate the interaction among pRB, CDK2 and CyclinE which prompts the transcription and translation of oncogenic C-myc. Strikingly, JMJD2A may trigger the demethylation of Pim1. Furthermore, Pim1 knockdown and P21(WAF1/Cip1) overexpression fully abrogated the oncogenic function of JMJD2A. JMJD2A promote liver cancer cell cycle progress through miR372-JMJD2AΔ- P21WAF1 /Cip1-Pim1- pRB-CDK2- CyclinE-C-myc axis.