Objective To investigate the immunological characteristics and predictive factors of chronic graft-versus-host disease (cGVHD) in children after haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HSCT) to provide a basis for early intervention. Methods A retrospective analysis was conducted on clinical and laboratory data of 64 children undergoing Haplo-HSCT. Peripheral blood lymphocyte subsets, immunoglobulins, and key components of the complement system were measured. Univariable and multivariable logistic regression analyses were used to identify predictors. Results The percentage of helper/inducer T lymphocytes and complement C3 levels were significantly higher in the cGVHD group (n=37) compared to the non-cGVHD group (n=27) (P<0.05), while the percentages of B cells and natural killer (NK) cells were significantly lower (P<0.05). Multivariate logistic regression identified the percentage of helper/inducer T lymphocytes (OR=1.144, P=0.012) and complement C3 level (OR=29.758, P=0.037) as independent predictors of cGVHD. Conclusions The development of cGVHD is closely associated with T-cell homeostasis imbalance, B-cell functional exhaustion, and abnormal activation of the complement system. The percentage of helper/inducer T lymphocytes and complement C3 levels may serve as potential predictive indicators for cGVHD occurrence.