Objective To investigate the types, clinical and imaging features and prognosis of chemotherapy-related cerebral lesion in acute lymphoblastic leukemia (ALL), so as to improve the clinicians' understanding of this kind of brain injury. Methods The clinical data of children with ALL who developed chemotherapy-related cerebral lesion after receiving chemotherapy alone from June 2015 to June 2023 were retrospectively analyzed. Results A total of 46 children (24 boys and 22 girls) with chemotherapy-related cerebral lesion were enrolled. The median onset age of ALL was 5.6(3.7-10.2) years old. The median age of children with cerebral lesion treated by chemotherapy was 6.6(4.7-10.3) years old. First cerebral lesion occurred 2.0(1.0-8.0) months after the first systemic chemotherapy, including 34 cases (73.9%) of encephalopathy, 9 cases (19.6%) of neurovascular complications, and 3 cases (6.5%) of isolated neurological symptoms. Neurological symptoms occurred in 38 children. Seizures were the most common (26 cases), followed by dizziness or headache, paralysis, visual disturbance, etc. The lesions in children with encephalopathy were mainly distributed around the lateral ventricles, semi-oval center, the parietal lobe, the occipital lobe, and the frontal lobe. The main neurovascular complications were intracranial hemorrhage and cerebral thrombosis, among which the superior sagittal sinus was the most common site of venous thrombosis.Among 38 patients with obvious neurological symptoms, 30 patients showed rapid improvement in clinical manifestations and had a good prognosis. At the follow-up of 22 months, 29 of the 32 children with neuroimaging abnormalities showed improvement after review. Conclusions The clinical and neuroimaging manifestations of ALL with chemotherapy-related cerebral lesion were diverse, and the overall prognosis was good. Few children had symptomatic epilepsy sequelae. Early neuroimaging is helpful for early detection and intervention of cerebral lesion and better optimization of ALL treatment.