Abstract: To screen differentially expressed genes in hepatocellular carcinoma (HCC) and evaluate the correlation between neurotensin (NTS) expression and inflammatory microenvironment genesis. Methods: Ten cases of primary HCC samples and corresponding adjacent tissues were collected, and total RNA was extracted for gene expression profiling using Affymetrix GeneChip® Human Genome U133 Plus 2.0. Thirty more cases of gene expression profiling data were downloaded from the GEO database and integrated with previous data to screen the differentially expressed genes using R2.9.0. The pathway analysis was conducted using MetaCore 2.5, Pathway Studio 6.0, and Ingenuity  1.0. Finally, the intensity of inflammation in situ was compared among 10 cases of HCC samples with different NTS expressions by H & E staining. Results: The RNA samples and bioinformatics data were of good quality. A distinct subgroup with high NTS expression, increased extracellular matrix reorganization, cell adhesion, leukocyte migration, and angiogenesis regulation was isolated from all 40 cases of HCC samples using SMA cluster and pathway analyses. More infiltrated inflammatory leukocytes and increased fibrogenesis and angiogenesis were observed in HCC samples with high NTS expression. Conclusion: Upregulated NTS expression may promote inflammatory microenvironment genesis in HCC.