Abstract： AIM To detect the expression of hypoxia inducible factor-1α (HIF-1α) in gastric malignant transformation in people from high altitude area of Qinghai,China.METHODS RT-PCR was used to detect the expression of HIF-1a gene in 7 cell lines and 27 pairs of GC and matched tumor adjacent normal gastric mucosa tissues.Using tissue microarray including 57 normal gastric mucosa tissues,37 chronic atrophic gastritis tissues,34 intestinal metaplasia tissues,and 146 gastric cancer (GC) tissues,immunohistochemistry (IHC) was performed to detect the level of HIF-1α protein expression.RESULTS The expression of HIF-1α at the mRNA level was different in GC cell lines.HIF-1α expression in AGS,SGC7901,and N87 cells was higher than that in MGC803,BGC823,PAMC82 and MKN45 cells.The level of HIF-1α expression was significantly higher in GC tissues (66.6％,18/27) compared with normal gastric mucosa tissues (26.3％,15/57;P ＜ 0.001).IHC data showed that the positive rate of HIF-1α was 64.8％ (24/37) in chronic atrophic gastritis tissues,61.7％ (21/34) in intestinal metaplasia tissues,and 56.8％ (83/146) in GC tissues,all of which were significantly higher than that in normal tissues (26.3％,15/57).Expression of HIF-1α was positively associated with age in GC (P ＜ 0.05).Kaplan-Meier analysis showed that patients with a low level of HIF-1α had apparently better survival than those with a high level (P ＜ 0.0001).HIF-1α protein (RR =3.229,95％CI:2.024-5.151) was identified to be an independent risk factor for the outcome of GC patients.CONCLUSION High HIF-1α expression is associated with gastric malignant transformation and poor prognosis in high altitude areas.