Background: In the hematology department, the availability of biomarkers for early detection of infection is difficult to obtain. The present study aimed to compare the diagnostic values of neutrophil CD64 Index, procalcitonin (PCT), interleukin-6 (IL-6) and C-reactive protein (CRP) and to determine whether the combined analysis of these biomarkers offer stronger predictive power in the diagnosis for the infection of febrile patients. Methods: Neutrophil CD64 Index, PCT, IL-6 and CRP levels were determined in 356 febrile patients in the hematology ward from May 2013 to May 2015. Sensitivity, specificity, positive and negative likelihood ratios, positive and negative predictive values, receiver operating characteristic (ROC) areas under the curve (AUC), and logistic regression analysis were determined to evaluate the diagnostic values of these biomarkers. Results: The levels of the four biomarkers were higher in the infection patients (p<0.001), and the PCT and IL-6 were higher in the patients with positive microbial blood culture (p<0.01). The neutrophil CD64 Index, PCT, IL-6, CRP had AUCs of 0.95, 0.83, 0.75 and 0.73, respectively. The best cut-off value of the neutrophil CD64 Index to detect infections was 5.06, with high specificity (87.5%) and sensitivity (88.4%). Furthermore, neutrophil CD64 Index, PCT and IL-6 offered the best combination of diagnosis with sensitivity of 93.9% and an AUC of 0.95. In addition, the neutrophil CD64 Index may have a special value to assist the physician to diagnose infection in the neutropenic patients with fever. Conclusions: The neutrophil CD64 Index is useful for early identification of infections in febrile patients in the hematology department. The combined analysis of the CD64 Index, PCT and IL-6 could further improve its sensitivity.