Midkine (MK) is a growth factor highly expressed in various cancers including neuroblastoma (NB). The plasma MK level is the reliable poor prognosis factor of NB. In addition, we reported that MK is involved in NB tumorigenesis in model mice, and also that it can be a potent therapeutic target. Here we have suggested that MK is involved in cisplatin resistance of NB cells. The cisplatin resistance of NB cells (TNB1, YT-nu, SH-SY5Y, SK-N-BE) were closely correlated with the expression levels of MK. In addition, because the knockdown of MK in TNB1 cells resulted in sensitization against cisplatin, it is suggested that MK is involved in cisplatin resistance of NB cells. In order to investigate the mechanism, we examined the expression level of cisplatin resistance-related genes including influx pumps, efflux pumps, neutralizing enzymes, DNA repairing enzymes and so on. As a result, some of them showed the correlation with MK expression. Their expressions were high in resistant TNB1 or YT-nu cells, and were decreased in response to knockdown of MK. These results suggest that MK would induce cisplatin resistance by regulating those genes. We previously reported that MK promotes cisplatin-induced nephrotoxicity by recruiting neutrophils, and that targeting MK can protect kidney from cisplatin. Taking this into consideration, the combination of cisplatin and MK targeting therapy could bring ideal effects: 1) cisplatin activity could be enhanced by the sensitization of NB cells, 2) nephrotoxicity could be prevented, 3) MK targeting could also exert antitumor effect independently of cisplatin.