Tart cherry (Prunus cerasus L.), a medicinal food containing high concentrations of phytochemicals, has a variety of antioxidant activities and health benefits. Here, we investigate the functional effect of tart cherry during apoptotic cell death elicited by airborne particulate matter with a diameter of <10 μm (PM₁₀) in human epidermal keratinocyte HaCaT cells. The PM₁₀ particles significantly induced cytotoxicity in the HaCaT cells. The decrease in cell viability was restored upon treatment with tart cherry extract (200 μg/mL) containing chlorogenic acid, quercetin, and kaempferol. Tart cherry inhibited the intracellular reactive oxygen species (ROS) responsible for the distinctive activations of the extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) in PM₁₀-treated HaCaT cells. Interestingly, tart cherry significantly inhibited the expression of apoptosis-related genes (B-Cell Lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), and caspase-3) as regulated by the activation of transcription factor nuclear factor-kappa B (NF-κB). These results demonstrate that tart cherry is a medicinal food that blocks the mitochondrial pathway of apoptosis induced by PM₁₀ in human epidermal keratinocytes.