Follistatin-like protein 1 (FSTL1) showed overexpression in the inflammatory synovial pannus, serum, and synovial tissues of osteoarthritis (OA) patients. However, FSTL1 knock out (KO) embryos exhibited reduced vertebral cartilage cellularity, extensive skeleton defects and reduced MSCs proliferation. Thus, the role of FSTL1 in chondrocyte proliferation is not completely understood. In vitro studies revealed that Human recombinant FSTL1 (hFSTL1) promoted chondrogenic signals in the MSCs and cell viability only at low concentrations. Recent reports suggest that high levels of FSTL-1 are proposed to enhance inflammatory signals which suppress chondrogenesis leading to cartilage destruction. Altogether, FSTL1 has the potential to promote MSC proliferation and chondrogenic differentiation in a low concentration-dependent manner. However, the mechanism by which FSTL-1 affects MSCs chondrogenic differentiation and chondrogenesis remains unknown. Therefore, this review introduces a deep discussion of FSTL1's molecular functions in the OA pathophysiology, which will contribute to the deep understanding of FSTL1 molecular activity in the OA pathogenesis.