Interferons are multifunctional cytokines widely used in clinical settings as an anti-viral drug. In addition, interferon’s exhibit anti-cancer and anti-bacterial effects. Nearly two thousand papers related to interferon are published each year, which illustrates the importance placed by researchers on the study of interferon. This review focuses on recent advances in the study of interferon, particularly in the areas of its mechanism of anti-cancer effect and signal transduction. We also describe the tumor resistance to interferon and the side-effect of interferon-based therapy, which leads to an expectation of future research of interferon.