Aim To screen miRNA for efficient regulation of LPA gene expression. Methods The miRNA of LPA gene 3′UTR were predicted by on-line prediction tools. The mRNA and protein expression of apolipoprotein(a) (Apo(a)) were detected by RT-PCR and Western blot after transfection. The experiment was divided into 4 groups:control group, miR-626 mimic group, miR-626 mimic+miR-626 inhibitor group and miR-626 inhibitor group. The miR-626 target validation assay was performed using a luciferase reporter system. Results There were 9 miRNA binding 3′UTR of LPA gene. Compared with the control group, the expression of Apo(a) mRNA was not significantly different between the mimic transfected group and the control group, but miR-626 significantly down-regulated the expression of Apo(a) protein. MiR-626 attenuated Apo(a) protein down-regulation by miR-626 inhibitor. The fluorescence intensity of the miR-626 cells was significantly lower than that of the control group after cell lysis. Conclusion MiR-626 down-regulates the expression of Apo(a) in HepG2 cells. MiR-626 down-regulates the expression of Apo(a) protein in LPA mRNA by direct binding to LPA mRNA 3′UTR.