Malignant glioma is the most common and fatal tumor in central nervous system, with the poor prognosis even with the advanced treatments.Seeking new prognostic factors and molecular targets may contribute to the understanding ofmalignance progression and patient treatment.Here, we investigated the neurotensin (Nts) expression in a series of 116 patients with gliomas of different histology grades and primary cultured glioma initiating cells (GICs).The correlation between Nts expression and the prognosis was analyzed.The effect of Nts expression on GICs proliferation was also detected.We found that NTS expression was detected in 70.9% of malignant gliomas and was significantly (P =0.015) related with a poor prognosis.Multivariate analysis indicated that Nts expression (P =0.007) was independent predictors of poor prognosis.Meanwhile, the results revealed that Nts was mainly expressed by GICs, not by differentiated glioma cells.Inhibition of Nts expression resulted in a significant reduction of GICs proliferation.Our study indicated that the expression of Nts positively correlated with the histology grades ofmalignances and could be identified as a prognostic marker in patients with glioma.Nts which are highly expressed in GICs promoted the proliferation of GICs in an autocrine fashion and might be a potential target to restrict self-renewal of GICs.