The development of resistance to cisplatin during treatment of testicular cancer constitutes a major obstacle to the cure of testicular cancer. To resolve its mechanism will provide useful information for making clinical decisions. We found 4 and 15 gene expressions were, respectively, up-regulated and down-regulated in cisplatin-resistant testicular cancer NEC-8/DDP cells compared with their parental NEC-8 cells (about 2.5-fold) using cDNA microarray analysis. After screening, we selected the ENTPD6 among these 19 genes. ENTPD6 was less expressed in cancerous region compared with that in non-cancerous lesion. In addition, ENTPD6 expression in seminoma was higher than that in other testicular tumors. ENTPD6 expression was involved in cellular sensitivity to cisplatin through an interaction with E-cadherin. ENTPD6 is a promising molecular biomarker of cisplatin resistance in testicular cancer, and also a novel therapeutical target modulating cisplatin resistance in testicular cancer.