Background: Many cytogenetic changes and gene mutations are associated with acute myeloid leukaemia (AML) survival outcomes. CD56 is related to poor prognosis when expressed in adult AML. The prognostic value of CD56 in children with AML has rarely been reported. Procedure: To evaluate the prognostic value of CD56 in childhood AML, multicentric retrospective study included 224 paediatric patients in two hospitals between January 2015 and April 2021. Results: The median (range) age was 75 (8-176) months, and the median follow-up time was 31 months. There was no significant difference in the 3-year overall survival rate between the CD56-positive and CD56-negative groups (78.4% vs. 73.3%, P=0.496). For patients who received haematopoietic stem cell transplantation, there was no significant difference in the 3-year overall survival rate between the CD56-positive and CD56-negative groups (59% vs. 63.9%, P=0.922). Multivariate analysis showed that CD56 positivity was not an independent prognostic factor for childhood AML (hazard ratio 0.85, P=0.648). Furthermore, in children with AML, CD56 positivity was more likely to be associated with the CBFβ-MYH11 mutation and mixed lineage leukaemia gene rearrangement. Conclusions: In summary, we demonstrated that CD56 cannot be used as a factor to predict the prognosis of children with AML.