BACKGROUND: One fifth of US counties are designated persistent child poverty counties (>/=20% of children in poverty since 1980). The association between a persistent child poverty environment and mortality in children with cancer is unknown. METHODS: Our cohort includes 2,089 children with cancer (2000-2016) in Alabama. We used multivariable cox proportional hazards modeling (adjusted for sociodemographics/clinical characteristics) to assess mortality by persistent child poverty designation at 1, 5 and 10 years from diagnosis. Distance to treatment was subsequently explored. RESULTS: Forty-two percent of the cohort lived in a persistent child poverty county; they were more likely to be African American (P<0.0001), have public/no insurance (P=0.0009), and live >100 miles to treatment (P<0.0001). Children in persistent child poverty counties were 30% more likely to die by 5 years (95%CI=1.06-1.59, P=0.012). Distance (per 20-mile increase) to treatment was associated with a 9% increased mortality risk (P<0.0001). Children with both exposures (distance >100 miles and persistent child poverty) faced the highest mortality risk at 5 years (HR=1.80, 95%CI=1.39-2.33, P<0.0001). In sub-analysis, children exposed to persistent child poverty were at higher risk for cancer-related mortality. However, the risk of health-related mortality did not differ. CONCLUSION: Among children with cancer from the Deep South, persistent child poverty was a prevalent exposure associated with inferior overall survival. Distance to treatment was independently associated with inferior survival. Children with both exposures had the highest risk of mortality. IMPACT: Persistent child poverty is associated with inferior survival among children with cancer; mechanisms underlying this disparity warrant investigation.