Abstract： Objective To study the effect of hypoxia-inducible factor la (HIF-1α) small interfering RNA (siRNA) combined with cisplatin on growth of human esophageal squamous carcinoma cells transplanted in nude mice. Methods Human esophageal squamous carcinoma TE-1 cells cultured in vitro were transplanted under the lateral skin of right upper limb in 12 nude mice to establish tumor-bearing models. Anti-tumor experiment was carried out. The nude mice were then divided into four groups (n=3 for each) to receive intratumor injection of normal saline (Group A), 20 mg/L cisplatin (Group B), 20 μmol/L HIF-1α siRNA (Group C) or both 20 mg/L cisplatin and 20 μmol/L HIF-1α siRNA (Group D). The volume of injected agent was 20 μl for each group. Change in tumor size was recorded every week. At week 3, all the nude mice were sacrificed and the transplanted tumor volume and weight were measured. In transplanted tumor of all the mice, the expression of HIF-1 α mRNA was detected by semi-quantitative RT-PCR and HIF-1 α protein was detected by immunohistochemistry. The apoptosis of TE-1 cells was determined by flow cytometry with Annexin V-FITC/PI dual staining. Results After anti-tumor experiment for three weeks, the transplanted tumor volumes of groups A,B,C and D were (1.477±0.132) cm~3, (1.200±0.114) cm~3, (1.223±0.129) cm~3 and (0.890±0.141) cm~3, and the tumor weight was (7.38±0.96) g, (6.35±0.73) g, (6.12±0.65) g and (3.51±0.42) g respectively. The rates of tumor suppression were 14.0%, 17.1% and 52.4% in groups B, C and D. Group D mice experienced strongest tumor suppression as compared with the other 3 groups (P<0.05). The expressions of HIF-1α mRNA and protein were down-regulated to 0.343±0,080 and 0.196±0.018 in Group C, 0.312±0.055 and 0.229±0.035 in Group D with no significant difference between these two groups (P>0.05), but were significantly different with those in Group A (mRNA 1.315± 0.179, protein 0.523±0.102) and Group B (mRNA 1.483±0.460, protein 0.542±0.174)(P<0.01). The rates of TE-1 cell apoptosis in groups A, B, C and D were (6.13±1.38)%, (28.30±4.82)%, (34.10±5.56)% and (52.88±8.77)% respectively, presenting a significant difference when comparing Group D with the other three groups (P<0.01). Conclusion HIF-1α siRNA can down-regulate HIF-1α mRNA and protein expressions in nude mice in vivo, induce cell apoptosis, significantly inhibit tumor growth of esophageal squamous carcinoma TE-1 cells, and improve the cytotoxicity of cisplatin chemotherapy.