The Wnt signaling pathway plays an important role in biological behaviors, such as embryonic development, tissue homeostasis, and tumor progression. The expression of Wnt signal was affected by many factors. The secreted frizzled-related protein (SFRPs) family is an important inhibitor of Wnt which extracellularly binds to Wnt or frizzled (Fz) receptor of Wnt to inhibit the transmission of Wnt signal. Secreted frizzled-related protein-3 (SFRP3) is the first discovered member of SFRPs. The silence of SFRP3 caused by the methylation of its promoter is closely relevant to the incidence and development of malignant tumors, so SFRP3 is often regarded as a tumor suppressor gene. The gene polymorphism of SFRP3 is also a high risk factor of some malignant tumors. This paper reviews research progresses of the relationship between SFRP3 and tumors.