To identify invasion-associated genes in extranodal natural killer (NK)/T-cell lymphoma, we performed microarray analysis on seven tumor samples and two control pools (composed of normal NK cells and T cells, tonsil and spleen) using Affymetrix GeneChip. Compared with all control pools, 59 uniquely expressed genes were discovered in the tumor samples. Overexpressed genes related to proteolysis, cell motility and chemotaxis, including CTSL, uPAR, TIMP-1, CXCL9, CXCL11 and DEFB1, were identified. Comparing the gene expression profiles of five upper aerodigestive tract (UAT) cases with two non-UAT cases, we found some overexpressed genes in non-UAT cases related to proteolysis and cell adhesion function, including matrix metalloproteinase 9 (MMP-9). Immunohistochemistry detection was performed on 34 paraffin sections to evaluate the expression of selected genes. A correlation of urokinase-type plasminogen activator receptor (uPAR) expression with MMP-9 expression was revealed. Analysis of prognosis demonstrated that expressions of MMP-2 and MMP-9 were closely correlated with a poor prognosis. These invasion-associated genes may become targets for diagnostic and therapeutic procedures.