Objective To analyze the clinical features of patients with dengue fever (DF) accompanied by platelet count (PLT) reduction and their characteristics of traditional Chinese medicine (TCM) syndrome differentiation and treatment. Methods The clinical data of 1 570 patients with confirmed diagnosis of DF collected from the Information Management System (HIS) of the Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine (TCM) from January 2013 to December 2017 were retrospective analyzed. According to the patients accompanied by platelet (PLT) reduction or not, they were divided into DF accompanied by PLT reduction group (1 211 cases) and non-PLT reduction group (359 cases); according to whether the cooling blood and dissipating blood stasis TCM (composed of red peony, peony bark, rehmannia root, salvia miltiorrhiza, rhinoceros horn, etc.) was used or not in TCM syndrome differentiation prescription, they were divided into cooling blood and dissipating blood stasis group (492 cases) and non-cooling blood and dissipating blood stasis group (719 cases). The differences in clinical characteristics, laboratory indicators, TCM syndrome differentiation and prescription characteristics in DF accompanied by PLT reduction group and non-PLT reduction group were compared and analyzed; the differences in changes of white cell counts (WBC) and PLT levels before and after treatment between cooling blood and dissipating blood stasis group and non-cooling blood and dissipate blood stasis group were compared and analyzed. Results The proportions of rash, hemorrhage, WBC reduction and aspartate transaminase (AST) elevation in DF accompanied by PLT reduction group were significantly higher than those in non-PLT reduction group [rash: 61.4% (744/1 211) vs. 14.8% (53/359), hemorrhage: 7.3% (89/1 211) vs. 1.1% (4/359), WBC reduction: 88.2% (1 068/1 211) vs. 60.4% (217/359), AST increased: 41.0% (497/1 211) vs. 29.5% (106/359)]; the PLT and WBC in the DF accompanied by PLT reduction group were significantly lower than those in the non-PLT reduction group [PLT (×109/L): 74.2±27.5 vs. 166.6±42.8, WBC (×109/L): 2.1±1.6 vs. 6.4±3.7, both P < 0.05], and AST in the DF accompanied by PLT reduction group were significantly higher than those in the non-PLT reduction group (U/L: 69.6±34.1 vs. 52.6±26.1, P < 0.05). The common syndrome of TCM syndrome differentiation in DF accompanied by PLT reduction group and non-PLT reduction group was mainly Wei-Qi syndrome [425 cases (35.1%) and 147 cases (40.9%) respectively]; Yinqiao powder was the main TCM prescription in the two groups [132 cases (10.9%) and 46 cases (12.8%) respectively]. In the comparisons between the cooling blood and dissipate blood stasis group and non-cooling blood and dissipate blood stasis group, there were no statistically significant differences in the proportion of combining use of drugs for increasing WBC and PLT and the levels of WBC and PLT after treatment (all P > 0.05). After treatment, the WBC, PLT levels and the proportions of above indexes returned to normal in the cooling blood and dissipate blood stasis group were significantly higher than those in the non- cooling blood and dissipate blood stasis group [WBC(×109/L): 4.5±3.1 vs. 3.2±2.4, proportion of WBC returned to normal: 42.7% (210/492) vs. 33.1% (238/719); PLT (×109/L): 85.9±26.2 vs. 79.3±24.8, proportion of PLT returned to normal: 41.1% (202/492) vs. 27.5% (198/719), all P < 0.05]. Conclusions The symptoms of skin rash and bleeding are more common in patients with DF accompanied by PLT reduction. The syndrome differentiation of TCM for this disease is mostly based on the combined disorders of Wei (defence) and Qi, both Qi and blood burning and blood stasis associated with toxin. Cooling blood and dissipating blood stasis may help the recovery of WBC and PLT in these patients, which is of great significance in reducing severity of dengue fever (such as bleeding).