Polycyclic aromatic hydrocarbons (PAHs), such as benzo(a)pyrene (BaP), are persistent environmental pollutants recognized for their high toxicity and resistance to microbial degradation. The marine yeast Debaryomyces hansenii has emerged as a compelling candidate due to its ability to thrive under a variety of stressful conditions. This study presents a molecular and biochemical analysis of the responses of D. hansenii to BaP exposure, providing insights into the detoxification and antioxidant mechanisms. In this study, we explored BaP removal from the medium and characterized the associated molecular and biochemical responses induced by this compound. Our findings demonstrate that D. hansenii can grow in BaP concentrations up to 100 ppm without compromising cell viability and is capable of biotransforming nearly 70% of the compound within 6 days. This process involved cytochrome P450 (CYP), epoxide hydrolase (EH), and glutathione S-transferase (GST), enzymes typically associated with xenobiotic metabolism. BaP exposure resulted in pronounced oxidative stress, evidenced by elevated ROS levels, lipid peroxidation, and protein carbonylation. However, D. hansenii activated a robust antioxidant defense, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and regulation of the glutathione redox system. Altogether, these results show that D. hansenii maintains redox homeostasis during BaP biotransformation through a coordinated enzymatic network that links xenobiotic metabolism with antioxidant protection, thereby expanding mechanistic understanding and providing a basis for future studies under environmentally relevant conditions.IMPORTANCEUnderstanding how marine yeasts respond to polycyclic aromatic hydrocarbons (PAHs) is important for advancing our knowledge of stress adaptation and xenobiotic biotransformation in extremophilic microorganisms. Debaryomyces hansenii is a suitable model organism because it naturally tolerates high salinity, oxidative conditions, and nutrient limitation. By characterizing its responses to benzo(a)pyrene (BaP), we can gain insight into how eukaryotic microbes activate biotransformation pathways and antioxidant defenses under chemical stress. This insight contributes to a broader comprehension of cellular strategies for coping with toxic contaminants and provides the basis for future applied research.