Background: Mothers of children with cancer often feel helpless in meeting their child's healthcare needs and in sustaining their family lives which increased during the pandemic. Aim: This study aimed to evaluate the effect of educational program for mothers of children with pediatric oncology regarding COVID-19 knowledge, attitudes, and practices. Method: A quasi-experimental (pre-post-test) research design was used. A convenience sample of 120 mothers of children who were diagnosed with cancer and admitted to the pediatric oncology department or attending the pediatric oncology outpatient clinic at South Egypt Cancer Institute in Assiut City. Three tools; Children and their mothers' characteristics, COVID-19 knowledge questionnaires and knowledge about attitude and practice toward COVID-19. Results: The study results detects that minority of mothers had a good score of knowledge before program increased to 95.0 % after program (p=<0.001**). Also, more than half of mothers had satisfactory knowledge about attitude and practice level before the program which reached 98.3% after program (p=< 0.001**). Conclusion: Mothers' knowledge significantly improved after the program application. Likewise, the mothers' knowledge about attitudes and practices toward COVID-19 changed positively and significantly enhanced after the educational program. Recommendations: Continued educational programs regarding COVID-19 help the mothers improve their knowledge, attitude and practices.