The development of resistance towards chemotherapeutic drugs has become an obstacle in treatment of cancer. Ankaferd Hemostat [ABS] has shown to suppress the proliferation of melanoma cells, but little is known about its’ mechanism. In this study, we demonstrate that ABS can make some melanoma cell lines such as A2058 more sensitive towards etoposide by altering the genes involved in oxidative phosphorylation [OXPHOS] pathway. ABS treatment has shown to increase the sensitivity of A2058 towards etoposide and showed no effect for SK-MEL-5. Previously known to be more resistant to etoposide, SK-MEL-30 showed least amount of sensitivity to ABS. We found mitochondrion cluster to be the most relevant to genes altered by ABS. To validate our claim, we compared two sets of melanoma cell lines; A375 with A2058 and A375 with SK-MEL-2. The clusters that we obtained from A375 and A2058 comparison did contain mitochondrial related clusters, their corresponding p value was not significant. Whereas, the clusters from A375 and SK-MEL-2 comparison contain 72 genes in ‘oxidoreductase’ cluster with enrichment score of 2.52. To get insight of the oxidoreductase cluster, we put the genes in that cluster to Enrichr. We found that majority of the genes among oxidoreductase cluster participate in oxidative phosphorylation and electron transport chain. Our study suggests that the use of ABS prior to etoposide treatment can increase the response of melanoma cell lines because of the alteration of OXPHOS genes.