Arsenic trioxide has been successfully introduced in the treatment of acute promyelocytic leukemia in the last years. It has led to a transformation of acute promyelocytic leukemia from being a highly fatal disease to one of the best curable hematologic malignancies. For this reason, the interest in arsenic trioxide as an anti-cancer drug has increased and experiments have been conducted to assess its applicability to other types of cancer. However, the results were quite disappointing. Therefore, this thesis aims to further elucidate the response of cells to arsenic trioxide on the protein level. To pursue this goal, HL-60 cells were treated with arsenic trioxide to shed light on the resulting proteomic changes. After arsenic trioxide treatment the proteins were isolated and enzymatically digested. This procedure was followed by a shotgun LC-MS/MS approach to analyze the proteins in the control and arsenic trioxide-treated group. The proteins found were identified via MaxQuant software and statistical testing was conducted using Perseus. Several significant changes in protein levels have been observed in this thesis. These changes depict the cells attempt to counter the induced oxidative stress by upregulation of proteins involved in redox homeostasis. Additionally, proteins associated with centrosome function and proteins implicated in NF-κB signaling were found to be differentially expressed. Furthermore, a shuttling of enzymes to the nucleus, implying epigenetic changes has been witnessed.