Ovarian cancer is the most lethal gynecologic neoplastic disease in which the molecular etiology remains largely unclear. Like other cancer types, evolution of ovarian tumor cell species is accompanied by acquisition of novel gene products and these new tumor-associated antigens elicit a host immune response that creates selection pressure upon the emerging tumor clones. One of the mechanisms that ovarian cancer cells evade immune surveillance is by upregulating human leukocyte antigen-G (HLA-G) expression. HLA-G is a non-classical MHC class I molecule and accumulated evidence has suggested its biological role in inactivating immune response. It has been well known that HLA-G expression is frequently detected in the most aggressive type of ovarian cancer, i.e., high-grade serous carcinoma, and measurement of HLA-G protein levels has shown promise for detection and prognosis prediction in ovarian cancer. This review summarizes those recent studies on HLA-G expression in ovarian cancer with special focus on its clinical and biological significance which is fundamental to elucidate the molecular mechanisms in ovarian cancer development and paves the foundation for future HLA-G-based diagnostics and therapeutics.