Objective To observe the clinical effect of benzene sulfonic amlodipine combined with traditional Chinese medicine (TCM) Yangxueqingnao granules for treatment of patients with hypertensive urgencies (HU) with acute headache, and its effect on serum brain derived neurotrophic factor (BDNF) level.Methods A prospective study was conducted, 186 HU patients with acute headache admitted to the Department of Cardiology in the Affiliated Hospital of Southwest University from January 2014 to December 2016 were enrolled, and they were divided into a control group (90 cases) and an observation group (96 cases) by random number table method. The patients in control group received benzene sulfonic amlodipine (10 mg, once a day) and the patients in observation group were additionally given Yangxueqingnao granules (4 g, 3 times a day for consecutive 7 days) on the basis of treatment in control group. The mean arterial pressure (MAP), the nature and location of headache and the levels of serum BNDF were examined before and after treatment and compared between them in the two groups, the degree of headache was evaluated by visual analogue scale (VAS), and the clinical therapeutic effects in the two groups were observed.Results There were no statistical significant differences in MAP (mmHg, 1 mmHg = 0.133 kPa) between the two groups before treatment and at 2 hours, on 1, 3, 7 days after treatment (control group: 99.7±9.5, 94.2±9.1, 88.6±7.6, 81.8±9.3, 75.6±5.3 respectively, the observation group: 95.4±13.5, 91.2±8.1. 88.9±8.7, 83.2±8.6, 77.2±4.8 respectively, allP > 0.05). Compared with the control group, after treatment for 1, 3, 7 days, the nature of acute headache (dull pain, distending pain) was relieved more significantly, the number of patients with whole head headache was decreased more obviously in observation group [dull pain (cases): 16, 8, 3 vs. 28, 24, 18, distending pain (cases): 11, 6, 2 vs. 22, 16, 10, whole head pain (cases): 12, 5, 3 vs. 26, 20, 16, allP < 0.05]. With the prolongation of treatment, the VAS scores in the two groups were gradually decreased, on 7 days after treatment they reached to the lowest levels, and the degree of descent in the observation group was more significant than that in the control group (0.5±0.4 vs. 1.4±0.9,P < 0.05); thelevels of serum BNDF in the two groups were gradually increased after the 1st day of treatment, reached to the highest level on 7 days after treatment,and the degree of increase in observation group was more obvious than that in the control group (ng/L: 24.8±2.3 vs. 17.8±2.2). The therapeutic effective rate of the observation group was significantly higher than that of the control group [70.8% (68/96) vs. 53.3% (48/90),P < 0.05].Conclusion The combination of benzene sulfonic amlodipine and Yangxueqingnao granules can effectively relieve the acute headache in HU patients, and its mechanism is related to the increase in expression of BDNF.