Objective To study the effect and underlying mechanism of boron neutron capture therapy (BNCT) on human melanoma cells.Methods The situation of boronophenylalanine (BPA) uptake of human melanoma cells A375 was detected and then the boron-10 (10B) enriched cells were irradiated by an in-hospital neutron irradiator (IHNI-1).The radiation sensitivity was measured using clonogenic survival assay,the proliferation was examined by MTT assay,apoptosis was determined using flow cytometry,and the protein expression of cytochrome C in cytosol and activation of caspase-9 was detected by Western blot.Results 10B concentration in A375 cells approached to (2.884 ± 0.148)μg/107 cells after 24 h culture with BPA,which met the requirement of BNCT.At 2.1 min after neutron radiation,the survival fraction of BNCT group was decreased to 58％ of control (t =2.964,P ＜ 0.05).At 24 h after BNCT,the cell viability was decreased to 83％ of control (t =3.286,P ＜ 0.05),the apoptosis ratio was (55.2 ± 7.9) ％ (t =9.754,P ＜ 0.05),and the protein level of cytochrome C in cytosol and the activativity of caspase-9 were also enhanced (t =7.625,8.307,P ＜ 0.05).Conclusions Human melanoma cells can be killed by BNCT due to apoptosis through a mitochondrial pathway.