Parkin plays an important role in regulating protein degradation and mitophagy in dopaminergic neurons. Deficiencies in Parkin expression or function result in cellular stress, degeneration, and eventual death of dopaminergic neurons, contributing to the development of Parkinson's disease. Conversely, overexpression of Parkin enhances neuronal survival. Therefore, understanding the mechanisms of Parkin regulation is gaining importance. In this study, we described, for the first time, the molecular mechanism by which the aryl hydrocarbon receptor (AHR) mediates the upregulation of Parkin in human SH-SY5Y neuroblastoma cells. Specifically, we demonstrate that the human Parkin gene (PRKN) is transcriptionally upregulated by AHR through two distinct pathways depending on the nature of the AHR ligand. The stress-inducing AHR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) indirectly promotes Parkin transcription by inducing the expression of activating transcription factor 4 (ATF4). This mechanism involves TCDD-mediated endoplasmic reticulum (ER) stress. On the other hand, kynurenine, a nontoxic AHR agonist, induces Parkin transcription by promoting AHR binding to the PRKN gene promoter without activating ER stress. Our findings demonstrate that AHR activation represents a potential pharmacological pathway to induce human Parkin. However, attention must be exercised regarding the nature of the AHR ligand to mitigate potential neurotoxic side effects.