Background: Low 6-mercaptopurine (6-MP) adherence (<95%) is associated with increased relapse in pediatric acute lymphoblastic leukemia (ALL). Stronger habit has been associated with higher adherence. Our objective was to examine the relationship of 6-MP adherence to habit strength and health-related quality of life (HRQOL) in children with ALL. Methods: A single-center, cross-sectional study of 52 participants: 11 patients (mean age 16±4, 45% Female) and 41 parents/caregivers (age 37±5, 80% Female). Participants completed Visual Analogue Scale (VAS _dose), Patient Reported Outcomes Measurement Information System (PROMIS) Medication Adherence Scale (PMAS), Self-Regulated Habit Index (SRHI), and PROMIS HRQoL measures. Descriptive statistics and spearman’s rho correlations were used. Eleven semi-structured interviews of participants were conducted and analyzed using Grounded Theory and thematic analysis. Results: Overall, 81% (42/52) of participants reported high 6-MP adherence (VAS _dose ≥95%): patients 91% (10/11) and parents 78% (32/41). Higher adherence was correlated with better peer relationship scores (r _s=0.34, P=0.03). No significant correlation was found between adherence and habit strength. Reported facilitators for higher 6-MP included reminders, care team communications, developing personalized tools, experience with medication administration, self-efficacy, and access to social support. On the other hand, financial burden, scheduling conflicts, and medication access were common barriers cited by participants. Conclusions: One-fifth of participants reported low 6-MP adherence, and habit strength wasn’t associated with adherence rates. Variability of 6-MP routines over treatment may prohibit automaticity. Behavioral interventions aimed at promoting habit formation could address barriers to 6-MP adherence and improve health outcomes in pediatric ALL.