Objective To explore the current status and influencing factors of parental burnout in parents of children with acute lymphoblastic leukemia (ALL), in order to provide references for clinical interventions. Methods A total of 259 parents of children with ALL treated in four tertiary hospitals in Guangzhou were surveyed using the general information questionnaire, Parental Burnout Assessment Scale, Mishel Uncertainty in Illness Scale, and Perceived Social Support Scale. Results The score of parental burnout in patients with ALL was (90.19±14.25) points. The severity of the child′s illness, the relationship with the child, family per capita monthly income, the total score of uncertainty in illness, and the total score of perceived social support were the main influencing factors for parenting burnout (all P<0.05), explaining 50.9% of the total variance. Conclusion Parents of children with ALL experience parental burnout. Increased attention should be given to parents of children with high disease severity, the mother of the child, lower family per capita monthly income, reducing the uncertainty in illness, and improving perceived social support to reduce the level of parental burnout.