Objective To evaluate the advantages and disadvantages of first-line empirical anti-infective therapy for patients with chemotherapy-induced febrile neutropenia of hematological malignancy. Methods Infection sites and distribution of pathogens of patients with chemotherapy-induced febrile neutropenia of hematological malignancy in a hospital from August 2017 to December 2018 were retrospectively analyzed, according to first-line anti-infective therapy scheme, patients were divided into carbapenem-based agents group(carbapenem group) and β-lactamase inhibitor compounds-based agents group(β-lactamase group), therapeutic efficacy, total hospitalization cost and length of hospital stay between two groups were compared. Results A total of 103 cases with chemotherapy-induced febrile neutropenia of hematological malignancy were collected, including 71 cases in carbapenem group and 32 cases in β-lactamase group. The most common infection site was respiratory tract, followed by bloodstream and gastrointestinal tract. 47 strains of pathogens were isolated, Gram-negative bacteria, Gram-positive bacteria and fungi accounted for 68.1%, 12.8% and 19.1% respectively, Klebsiella pneumoniae accounted for the highest proportion (25.5%), followed by Escherichia coli (21.3%) and Pseudomonas aeruginosa (8.5%). The effective therapeutic rates of carbapenem group and β-lactamase group were 90.1% and 71.9% respectively, the total hospitalization cost were (59 529.7±39 771.3) Yuan and (49 546.9±31 641.1) Yuan respectively, length of hospital stay were (28.7±7.9) and (26.2±6.3) days respectively, differences in therapeutic rate between two group of patients was statistically significant(P=0.038), differences in total hospitalization cost and length of hospital stay between two group of patients were not statistically significant (both P>0.05). Conclusion For patients with chemotherapy-induced febrile neutropenia of hematological malignancy, first-line empirical application of carbapenems as the main anti-infective therapy is better than β-lactamase agents, the total hospitalization cost and length of hospital stay of two groups have no significant difference.