Abstract: The human Fibulin protein family includes seven extracellular matrix proteins with similar structures. These proteins play important roles in the formation and stability of the extracellular matrix; the major components of this matrix are composed of elastic fibers and the basement membrane. In addition to their significant roles in formation of the extracellular matrix, the Fibulin family proteins regulate cell adhesion, growth, migration, and proliferation. Recent research confirmed that Fibulin family proteins play a significant role in tumor suppression and oncogenic activities as well as tumor invasion, proliferation, and prognosis. In this review, we summarize the functions and mechanisms of the Fibulin protein family in various tumors, with the goal to identify a novel biomarker for tumor therapy.