Abstract： Objective： To observe the clinical effect of the therapy of acupuncture combined with acupoint application on middle-advanced esophageal carcinoma and its effects on transforming growth factor- β1 (TGF- β1)/defect factor of cancer of pancreas (Smad) signal pathway. Methods： A total of 90 patients with middle-advanced esophageal carcinoma were randomly divided into the control group and the treatment group，with 45 cases in each group. The control group was given routine chemoradiotherapy for treatment， and the treatment group was additionally treated with acupuncture combined with acupoint application based on the treatment of the control group. The clinical effects and incidence of adverse reactions in the two groups after treatment，and the survival rates of patients after three years of follow-up were observed；the scores of Quality of Life Core Questionnaire 30 (QLQ-C30) and SF-36 Health Survey [physical component summary (PCS)， physical social summary (PSS) and mental component summary (MCS)]， and the levels of serum tumor markers [carbohydrate antigen 19-9 (CA19-9)， carcinoembryonic antigen (CEA)，cytokeratin 19 fragment 21-1 (CYFRA21-1) and carbohydrate antigen 125 (CA125)]，serum gastrointestinal hormones [vasoactive intestinal peptide (VIP)， somatostatin (SOM)， motilin (MTL) and 5- hydroxytryptamine (5-HT)] and TGF-β1/Smad signal pathway in supernatant liquid of wedge-shaped tissue (TGF-β1 RⅠtype receptor，TGF-β1RⅡ type receptor，Smad4 and Smad7) before and after treatment were also observed. Results：After treatment，the disease control rate was 95.24% in the treatment group，and 73.17% in the control group， the difference being significant (P＜0.05). After one and two courses of treatment，the scores of PCS，PSS and MCS in the two groups were increased when compared with those before treatment (P＜0.05)， and above three scores in the treatment group at the same time point were higher than those in the control group (P＜0.05). After one and two courses of treatment， the QLQ-C30 score in the treatment group at the same time point was lower than that in the control group (P＜0.05)，and there was no significant difference being found in the comparison of QLQ-C30 score in the control group before and after treatment (P＞0.05). After one and two courses of treatment，the levels of CA19-9，CEA (except the CEA in the control group after one course of treatment)， CYFRA21-1 and CA125 in the two groups were decreased when compared with those before treatment (P＜0.05)，and the above four levels in the treatment group at the same time point were lower than those in the control group (P＜0.05). After one and two courses of treatment，the levels of VIP，SOM and 5-HT in the two groups were decreased when compared with those before treatment (P＜0.05)， and the MTL levels were increased when compared with those before treatment (P＜0.05)；the levels of VIP，SOM and 5-HT in the treatment group at the same time point were lower than that those in the control group (P＜0.05)，and the MTL level was higher than that in the control group (P＜0.05). After one and two courses of treatment，the levels of TGF- β1RⅠtype receptor，TGF-β1 RⅡ type receptor，Smad4 and Smad7 in the treatment group were decreased when compared with those before treatment (P＜0.05)，and the above four levels at the same time point were lower than those in the control group (P＜0.05)，and there was no significant difference being found in the comparisons of levels of TGF-β1 RⅠtype receptor，TGF-β1RⅡ type receptor and Smad7 in the control group before and after treatment (P＞0.05). The control group only had significantly lower levels of Smad4 after two courses of treatment compared to before treatment. After three years of follow-up，the survival rate was 78.57% in the treatment group，and 56.10% in the control group，the difference being significant (P＜0.05). During treatment， the incidence of bone marrow suppression， toxic reaction of skin and digestive tract reaction in the treatment group was respectively lower than that in the control group (P＜ 0.05)；there was no significant difference being found in the comparison of incidence of injuries of bladder， kidney and heart function (P＞0.05). Conclusion： The therapy of acupuncture combined with acupoint application can significantly enhance the survival time and survival quality of patients with middle-advanced esophageal carcinoma receiving chemotherapy， and improve the levels of serum tumor markers and gastrointestinal hormones with great safety，whose mechanism may be related to the regulation of TGF-β1/ Smad signal pathway.