Objective To explore the relationship between serum ferritin (SF) and the treatment response, clinical risk and prognosis in children with acute lymphoblastic leukemia (ALL). Methods Clinical data and SF levels and bone marrow examination at 4 time points, i.e., first diagnosis (T1), before early enhancement (T2), before consolidation therapy (T3), and before maintenance therapy (T4) of 87 children with ALL admitted from October 2014 to January 2021 were collected. Results Among the 87 patients, 68 (78.16%) survived without incident for 3 years, and 19 (21.84%) with poor prognosis; the SF level of children in the poor prognosis group (269.24±79.25) was significantly higher than that of the accident-free survival group (174.06±51.12), and the difference was statistically significant (P <0.05). The average SF level of children in the high-risk group (232.86±64.28) was higher than that of the non-high-risk (low risk and intermediate risk) group (172.73±53.87), and the difference was statistically significant (P<0.01). At T1 and T2, there was no statistically significant difference in SF levels between the high-risk group and the non-high-risk group (P>0.05). But at T3 and T4, the SF level of children in the high-risk group was significantly higher than that of the non-high-risk group, and the difference was statistically significant (P<0.01); At T3 and T4, the SF level of the children in the high-risk group was higher than that of the same group at T1, the difference was statistically significant (P<0.01). High-risk children with high level ferritin were less responsive to treatment than high-risk children with normal ferritin, that is, before maintenance treatment the total number of positive minimal residues, positive fusion genes, recurrences and deaths in the ferritin overdose group (72.72%) was significantly higher than those of ferritin normal group (28.57%), and the difference was statistically significant (P<0.05). Conclusion Ferritin excess is related to poor response to treatment in children with ALL, and it is one of the risk factors for poor prognosis of ALL. In order to improve the treatment effect of children with ALL, it is recommended to dynamically monitor SF levels during chemotherapy.