Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, with limited treatment options and poor clinical outcomes. Dihydroartemisinin (DHA), have shown anti-tumor activity in UM, though typically at high concentrations. This study investigates the synergistic anti-tumor effects of combining DHA with a mitochondrial uncoupler CCCP. We treated UM cells with DHA and/or CCCP, and then proteomic profiling was performed to elucidate molecular mechanisms underlying the enhanced efficacy of the combination treatment. Our results indicate that co-treatment induces endoplasmic reticulum stress and activates autophagic cell death pathways, highlighting a potential combinatorial therapeutic strategy for UM.