This study aimed to evaluate the efficacy and safety of dexamethasone pretreatment regimen with different doses in the prevention of docetaxel-induced hypersensitivity reaction (HSR). One hundred and sixty-two patients who had malignant tumors as determined by histology and/or cytology and received docetaxel treatments at least 2 cycles, were randomized into two groups. There were 90 patients in the study group and 72 patients in the control group. In the study group, patients received 4.5mg of oral dexamethasone once a day. Patients in the control group received 8 mg of dexamethasone twice a day. All patients received dexamethasone for 3 days, from the day before docetaxel treatment to the day after docetaxel treatment. The endpoints were hypersensitivity reaction (HSR) and other adverse effects, which were determined according to common terminology criteria for adverse event v3.0 (CTCAE 3.0). In the study group, 10 patients had HSRs (11.1%). While in the control group, 7 patients had HSRs (9.7%), and the main clinical symptoms of HSR were rash (3.1%), fever/chill (2.5%), angioedema (1.9%), chest discomfort (1.9%) and hypotension (0.6%). There was no statistically significant difference between these two groups (P=0.774). There was no significant difference in the incidence rate of adverse effect between patients in the study group and in the control group. Those adverse effects included neutropenia, decreased hemoglobin, nausea, vomiting, fatigue and fluid retention. Since no significant difference in the HSR incidence between these two groups has been found, 4.5mg of dexamethasone (qd) is as efficient and safe as 8mg (bid).