Objective:To investigate the mechanisms underlying the effects of microRNA-449a(miR-449a)on proliferation and suppression of neuroblastoma. Methods:After overexpressed miR-449a in BE(2)-C cells,the change of gene expression levels were analyzed by quantitative real-time PCR(qPCR),cell viability was tested by MTT,and the proliferation efficiency of tumor cell was observed by clone formation assay. Meanwhile,we also predicted potential target genes of miR-449a using miRDB,and manipulated the level of MDM4 by overexpression or knockdown the expression of MDM4. Then,the expression of related proteins was analyzed by Western blot and the apoptosis was detected by flow cytometry. Results:Overexpression of miR-449a inhibited cell proliferation and colony formation,and promoted cell apoptosis. MDM4 was confirmed to be a target gene of miR-449a by using software prediction and the experimental verification. In addition,knockdown of MDM4 expression inhibited cell proliferation and colony formation. Overexpression of MDM4 neutralized the increases of apoptosis and p53 protein level induced by miR-449a. Furthermore,miR-449a promoted apoptosis of BE(2)-C cells,but this effect was not observed in p53 knockdown cell line. Conclusion:miR-449a increases p53 protein level by suppressing MDM4 to promote neuroblastoma cell apoptosis. This study implies miR-449a could be a potential therapeutic target of neuroblastoma.