Abstract: OBJECTIVE To explore the clinical value of C-reactive protein (CRP) and procalcitonin (PCT) in guidance to antibiotics usage for acute febrile patients so as to provide guidance for clinical diagnosis and treatment of the patients with acute fever. METHODS A total of 99 fever patients who were treated in the emergency department from Dec 2012 to Dec 2014 were recruited as the study objects and divided into the conventional treatment group, CRP group, and PCT group, with 33 cases in each group. The conventional treatment group was treated with antibiotics based on the doctor's experience and result of clinical laboratory test, the CRP group was treated with antibiotics according to the CRP level, and the PCT group was treated with antibiotics based on the PCT level. The time of use of antibiotics, cumulative DDDs, cost of antibiotics, days of hospitalization, hospitalization cost, and total effective rate of clinical treatment were observed and compared among the three groups of patients. RESULTS The time of use of antibiotics of the CRP group and PCT group were respectively (9.10±2.12) days and (9.11±2.18) days, significantly shorter than (14.32±6.32) days of the conventional treatment group; the cumulative DDDs of the CRP group and PCT group were respectively (18.23±6.32) and (18.89±7.01), significantly higher than (13.01±2.11) of the conventional treatment group; the cost of antibiotics of the CRP group and PCT group were respectively (4123.08±128.02) yuan and (4208.27±182.34) yuan, significantly cheaper than (6999.23±239.23) yuan of the conventional treatment group; the length of hospitalization of the CRP group and PCT group were respectively (9.01±1.11) days and (8.89±1.02) days, significantly shorter than (12.34±4.33) days of the conventional treatment group; the hospitalization cost of the CRP group and PCT group were respectively (6932.34±172.34) yuan and (6980.32±193.34) yuan, significantly less than (9443.23±342.34) yuan of the conventional treatment group. The total effective rate of clinical treatment of the CRP group was 93.94%, of the PCT group was 96.97%, of the conventional treatment group was 90.91%, respectively, and there was no significant difference. CONCLUSION CRP and PCT have great clinical significance in guidance of antibiotics usage for the acute febrile patients during the clinical diagnosis and treatment, and they are the ideal choice for clinical practice.