Gastric cancer is one of the most common aggressive malignancies with high incidence and mortality. Increasing evidence has suggested that microRNAs (miRNAs) are involved in the initiation and development of gastric cancer. Here, we found that miR-1179 was significantly down-regulated in both gastric cancer tissues and cell lines. Decreased expression of miR-1179 was remarkably correlated with the increased tumor size, higher tumor stage and lymph node metastasis of gastric cancer patients. Overexpression of miR-1179 significantly inhibited the proliferation and invasion of gastric cancer cells. Further molecular experiments showed that miR-1179 bound the 3'-untranslated region of the high mobility group box 1 (HMGB1) and decreased the expression of HMGB1 in gastric cancer cells. The level of HMGB1 was negatively correlated with the expression of miR-1179 in gastric cancer tissues. Rescue experiment demonstrated that restore the expression of HMGB1 significantly inversed the inhibitory effect of miR-1179 on the proliferation of gastric cancer cells. Our results uncovered the novel function of miR-1179/HMGB1 axis in the progression of gastric cancer.