Interleukin-18 (IL-18) is an immune-stimulatory cytokine with antitumor activity in preclinical models. Itplays pivotal roles in linking inflammatory immune responses and tumor progression and is a useful candidatein gene therapy of lymphoma or lymphoid leukemia. A phase I study of recombinant human IL-18 (rhIL-18) inpatients with advanced cancer concluded that rhIL-18 can be safely given in biologically active doses to patientswith advanced cancer. Some viruses can induce the secretion of IL-18 for immune evasion. The individualcytokine activity might be potentiated or inhibited by combinations of cytokines. Here we focus on combinationaleffects of cytokines with IL-18 in cancer progression. IL-18 is an important non- invasive marker suspected ofcontributing to metastasis. Serum IL-18 may a useful biological marker as independent prognostic factor ofsurvival. In this review we cover roles of IL-18 in immune evasion, metastasis and angiogenesis, applicationsfor chemotherapy and prognostic or diagnostic significance.