Objective To compare the curative effect of amphotericin B and voriconazole on fungal infection in children with acute lymphoblastic leukemia(ALL) during chemotherapy.Methods A total of 82 children with fungal infection during ALL chemotherapy were enrolled and randomly divided into group A(n=41) and group B(n=41) from March 2018 to March 2024, 41 cases in each group. Group A was treated with amphotericin B, while group B was treated with voriconazole. The curative effect after treatment, inflammatory factors ［C-reactive protein(CRP), tumor necrosis factor-α(TNF-α), procalcitonin (PCT)］ and T lymphocyte subsets(CD3+, CD4+, CD8+, CD4+/CD8+) before and after treatment, and occurrence of adverse reactions(visual reactions, gastrointestinal adverse reactions, liver-kidney function damage, neurotoxicity) during treatment in the two groups were compared. Results The total response rate of group B was better than that of group A(87.80% vs65.85%, P<0.05). After treatment, CRP, TNF-α and PCT in group B were lower than those in group A(P<0.05), CD3+, CD4+, CD8+ and CD4+/CD8+ were higher than those in group A(P<0.05), and incidence of adverse reactions was lower than that in group A(26.83% vs 48.78%, P<0.05). Conclusion Compared with amphotericin B, curative effect of voriconazole is better on fungal infection in ALL children during chemotherapy, which can reduce inflammatory response and enhance immunity, with fewer adverse reaction