The aggressive nature of metastatic human cancer has been shown to be related to numerous abnormalities in growth factors and their receptors. These perturbations confer a tremendous growth advantage to the malignant cells. Interleukin-8 (IL-8), originally discovered as a chemotactic factor for leukocytes, has recently been shown to contribute to human cancer progression through its potential functions as a mitogenic, angiogenic, and motogenic factor. While it is constitutively detected in human cancer tissues and established cell lines, IL-8 expression is regulated by various tumor microenvironment factors, such as hypoxia, acidosis, nitric oxide, and cell density. Understanding the mechanisms of both inducible and constitutive IL-8 expression will be helpful in designing potential therapeutic strategies of targeting IL-8 to control tumor growth and metastasis. In this review, the role and regulation of IL-8 expression in the growth and metastasis of human cancer with a focus on human pancreatic adenocarcinoma will be discussed.