PURPOSE: WeChat-based education and care program serves as a promising nursing method for relieving mental stress in parents of pediatric patients. This study purposed to explore the influence of the WeChat education and care program (WECP) on mental health, insomnia, and general state of health in parents of pediatric acute lymphoblastic leukemia (ALL) patients. METHODS: Totally, 146 parents of 73 primary pediatric ALL patients were randomized into the WECP group (74 parents of 37 patients) and standard care (SC) group (72 parents of 36 patients) to receive a 6-month corresponding intervention. Self-rating anxiety scale (SAS), self-rating depression scale (SDS), Athens insomnia scale (AIS), and 12-item general health questionnaire (GHQ-12) were assessed in parents of patients. RESULTS: SAS scores at the third month (M3) (P = 0.041) and M6 (P = 0.032) were reduced in WECP group versus SC group. SAS-defined anxiety rate at M6 (P = 0.035) was declined in WECP group versus SC group. SDS score at M6 was descended in WECP group versus SC group (P = 0.024). However, there was no discrepancy in SDS-defined depression rate at any time point between groups (all P > 0.05). AIS scores at M1 (P = 0.015) and M6 (P = 0.021), as well as GHQ-12 scores at M3 (P = 0.007) and M6 (P = 0.001) were decreased in WECP group versus SC group. By subgroup analyses, WECP exhibited good effects at M6 in mothers, but not in fathers. CONCLUSION: WECP is a feasible and efficacy intervention to improve mental stress and health status among parents of pediatric ALL patients, especially in mothers.