〔Abstract〕 Objective To explore the clinical effect of the empirical treatment of carpofungin combined with itraconazole in patients with neutrophil deficiency and fever. Methods A total of 120 patients with neutrophilia deficiency and fever during hematologic tumor treatment in Yangjiang People's Hospital from May 2020 to February 2022 were selected and divided into a control group and an observation group according to random number method, with 60 cases in each group. The control group was treated with carpofungin, and the observation group was treated with itraconazole on the basis of the control group. The clinical efficacy, clinical indicators, levels of inflammatory factors, clearance rate of pathogenic bacteria, fever-reducing rate and survival rate, toxicity and side effects were compared between the two groups. Results The total clinical effective rate of the observation group was higher than that of the control group, the difference was statistically significant (P < 0.05). The time of fungal pathological transition to negative, fever remission and hospital stay in the observation group were shorter than those in the control group, and the differences were statistically significant (P < 0.05). After treatment, the serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP) and procalcitonin (PCT) in the observation group were lower than those in the control group, and the differences were statistically significant (P < 0.05). The pathogenic bacteria clearance rate, febrile regression rate and survival rate in the observation group were higher than those in the control group, and the differences were statistically significant (P < 0.05). The total incidence of side effects in the observation group was lower than that in the control group, and the difference was statistically significant (P < 0.05). Conclusion The empirical treatment of carpofungine combined with itraconazole in patients with neutrophil deficiency and fever is helpful to improve the clinical effect, reduce the level of inflammatory factors, improve the fever reduction rate, pathogen clearance rate and survival rate of patients, and promote the recovery of patients, with relatively high safety.