Objective To provide evidence for TCM treatment according to syndrome differentiation by studying the correlation between TCM syndromes and serum gastrin (GAS), motilin (MTL), cholecystokinin (CCK) and vasoactive intestinal peptide (VIP) levels of reflux esophagitis (RE) patients. Methods A total of 120 eligible RE patients from Dongzhimen Hospital were differentiated with TCM syndromes, and blood samples were taken to test for GAS, MTL, CCK and VIP levels. Differences between the different TCM syndromes in terms of serum gastrointestinal hormones levels were analysed. Results The male patients had the most distribution of stagnation of heat in the liver and stomach syndrome, but the female patients had the most distribution of disharmony of the liver and stomach syndrome (χ2=27.994, Ps<0.001). The Grades A, B and C were mainly associated with the obstruction of phlegm syndrome, disharmony of the liver and stomach syndrome, and stagnation of heat in the liver and stomach syndrome respectively (χ2=9.951, P=0.007). For patients with the syndrome of stagnation of heat in the liver and stomach, the serum GAS level was significantly lower than the syndrome of disharmony of the liver and stomach, the syndrome of obstruction of phlegm, the syndrome of deficiency of the center and upward flow of qi, and mixture of cold and heat syndrome (P<0.01 or P<0.05). For patients with mixture of cold and heat and patients with deficiency of qi and stagnation of blood, there was a significant raise in serum CCK level, compared to the patients with stagnation of heat in the liver and stomach, patients with disharmony of the liver and stomach, or patients with deficiency of the center and upward flow of qi (P<0.01). Compared with the patients with disharmony of the liver and stomach and patients with the syndrome of obstruction of phlegm, the serum CCK level of patients with the syndrome of deficiency of the center and upward flow of qi rose significantly (P<0.01). Compared with the patients with the syndrome of stagnation of heat in the liver and stomach, the serum MTL levels of patients with obstruction of phlegm and patients with mixture of cold and heat rose significantly (P<0.01). There was a significant raise in serum MTL level of patients with the syndrome of mixture of cold and heat compared to patients with disharmony of the liver and stomach and patients with deficiency of the center and upward flow of qi (P<0.05). Conclusions The RE patients with mixture of cold and heat, and patients with deficiency of qi and stagnation of blood, and patients with deficiency of the center and upward flow of qi may be related to the rise in CCK levels. The patients with the syndrome of stagnation of heat in the liver and stomach are related to the decrease in GAS and MTL levels.