Aim To study the regulatory effect of apolipoprotein(a) (Apo(a)) expression in HepG2 cells by maternal gene 3 (MEG3) and its mechanism. Methods The targeted binding of MEG3 to miR-125a-5p was analyzed using the luciferase reporter enzyme system. Real-time quantitative PCR (qRT-PCR) was used to detect the expression of MEG3 in HepG2 cells with high expression of Apo(a) and SMMC7721 cells with low expression of Apo(a); MEG3 was transfected into HepG2 cells, and expression of Apo(a) and TET2 were detected by Western blot and qRT-PCR. TET2 expression was silenced using small interfering RNA technology. Results MEG3 and hsa-miR-125a-5p could complement each other. Systematic analysis of luciferase reporter gene confirmed the presence of MEG3 binding to hsa-miR-125a-5p. miRNA microarray results showed that the expression level of hsa-miR-125a-5p increased in HepG2 cells, which was nearly 1.5 times higher than that in the control group. Both HepG2 cells and SMMC7721 cells expression MEG3, but the expression level of MEG3 in HepG2 cells is significantly lower than SMMC7721. MEG3 transfection inhibited Apo(a) expression. Mechanism study found that, MEG3 downregulated the expression of miR-125a-5p and upregulated TET2 expression; miR-125a-5p mimics reversed the effect of MEG3, but can be reversed by inhibitors of miR-125a-5p; TET2 silencing can reverse the downregulation Apo(a) expression effect of MEG3. Conclusion MEG3 downregulates the expression of Apo(a) in HepG2 cell through miR-125a-5p/TET2 pathway.