Abstract Gamma delta T-cell acute lymphoblastic leukemia (γδ T-ALL) represents a rare subset of T-ALL and is correlated with high rates of induction failure, relapse and increased mortality. γδ T-ALL lacks a biologically-informed framework for guiding its classification and treatment strategies. In this report, we detail a case of child with γδ T-ALL who underwent induction chemotherapy and intensification treatment, followed by haploidentical hematopoietic stem cell transplantation. The patient achieved a clinical complete remission and remains minimal residual disease negative with chidamide maintenance post-transplantation. Single-cell RNA sequencing revealed a connection between histones HIST1 genes and gamma delta T-ALL, and identified potential effector functions of γδ T cells in combating this leukemia. This case carries significant implications for managing γδ T-ALL, highlighting the relationship between histone modification patterns and gamma delta tumor infiltrating lymphocytes in γδ T-ALL cells for developing novel therapeutic approaches.