PurposeDue to the emergence of multidrug resistance (MDR), traditional antileukemia drugs no longer meet the treatment needs. Therefore, new antileukemia drugs with different action mechanisms are urgently needed to cope with this situation.Materials and methodsArminin 1a-C is an antimicrobial peptide (AMP) developed from the ancient metazoan marine Hydra. In this study, we first explored its antileukemia activity.ResultsOur results showed that Arminin 1a-C formed an α-helical structure and efficaciously suppressed the viability of leukemia cell lines whether or not they were multidrug resistant or sensitive, and there were no obvious differences between these cell lines. Arminin 1a-C exhibited distinct selectivity between noncancerous and cancerous cell lines. Arminin 1a-C interfered with K562/adriamycin (ADM) cell (a kind of multidrug-resistant leukemia cell line) proliferation in a very rapid manner and formed pores in its cell membrane, making it difficult to develop resistance against Arminin 1a-C.ConclusionOur data show that Arminin 1a-C possesses great potential as a therapeutic candidate for the treatment of multidrug-resistant leukemia.