The aim of the present study is to assess mothers' knowledge and practices regarding care of their children suffering from acute leukemia undergoing chemotherapy, establish and implement a health educational program for mothers based on their needs, data obtained and reviewing literature and evaluate the outcome of the health educational program directed towards the mothers of acute leukemia children undergoing chemotherapy. The study conducted at the pediatric oncology out patient clinics at the waiting areas in the specialized pediatric hospital in Benha city, which this is the only established known place in kalubyia governorate that provides care to such children. A quasi experimental design was utilized to conduct the study. The study involved (53) children suffering from acute leukemia undergoing chemotherapy and accompanying their mothers and attending the out patients clinics for follow up and treatment. Two tools were used for data collection an interviewing questionnaire to assess the children's and their mothers' socio-demographic data, also the mothers' knowledge and an observation checklists to assess the mothers' practices towards care of their acute leukemic children undergoing chemotherapy. The findings showed that after the program implementation there was a significant improvement of mothers' knowledge and practices regarding care of their acute leukemic children undergoing chemotherapy. The study recommended that, continuous health education for mothers caring of acute leukemic children at home based on their needs and teaching them the principles of care for problems emerged as a result of their children disease and its related therapy.