Introduction Validated tools to measure caregiving knowledge among parents of children with hematological cancers are needed to measure the clinical outcome of caregiver interventions. This study reports the development and validation of the Hematological Oncology Parents Education Caregiving Knowledge Questionnaire (HOPE-CKQ) among Malaysian parents of pediatric leukemia and lymphoma patients. Methods Initially, 60 items on caregiving knowledge were developed based on a qualitative needs assessment study. Content validity was evaluated using item content validity index (I-CVI) and scale content validity index (S-CVI/Ave). Parents of pediatric leukemia and lymphoma patients were invited to complete the 60-item version of the HOPE-CKQ. Exploratory factor analysis (EFA) using polychoric correlation resulted in an 18-item version of HOPE-CKQ. Confirmatory factor analysis (CFA) was used to verify the factor structure. Known-group validity was tested by comparing the scores among different levels of parent education. Results The I-CVI ranged from 0.83 to 1.00 whereas the S-CVI/Ave was 0.99, indicating good content validity. A total of 167 complete responses were analyzed for factor analysis. EFA using polychoric correlations resulted in a single-factor structure consisting of 18 items. CFA confirmed that the 18-item single-factor HOPE-CKQ model had a good fit for the data. The internal consistency reliability was good (α=0.80). Parents with tertiary education level had higher caregiving knowledge (M=12.61, SD=3.37) compared to parents with secondary education and below (M=10.33, SD=3.80) (t=3.58, p<0.001). Conclusions The 18-item HOPE-CKQ is valid and reliable for use to measure caregiving knowledge among pediatric leukemia and lymphoma parents. This tool may be considered to measure caregiving knowledge in future preventive and intervention programs.