Atherosclerosis is one of the primary causes that lead to cardiovascular disease. LncRNAs have been regarded as key modulators in many pathological processes. The study aims to identify the regulatory role of LncRNA fetal-lethal noncoding developmental regulatory RNA (FENDRR) in atherosclerosis. Cell viability, proliferation, cell cycle and cell apoptosis were evaluated by Cell Counting Kit-8 (CCK-8) assay, flow cytometric analysis and western blot analysis. Quantitative real-time PCR (qRT-PCR) was carried out to determine FENDRR expression in PDGF-BB/TNF-alpha induced VSMCs. Levels of TNF-alpha, IL-1, IL-6, MCP-1 and ICAM-1 were investigated by enzyme-linked immunosorbent assay (ELISA). The results showed that cell viability was enhanced and FENDRR expression was downregulated after VSMCs were induced by platelet derived growth factor BB (PDGF-BB) or tumor necrosis factor alpha (TNF-alpha). Cell proliferation was inhibited by FENDRR overexpression in a time-dependent manner in PDGF-BB or TNF-alpha induced VSMCs. Moreover, FENDRR overexpression blocked cell cycle, suppressed the generations of TNF-alpha, IL-1, IL-6, MCP-1 and ICAM-1, and facilitated cell apoptosis in VSMCs induced by PDGF-BB or TNF-alpha. These findings indicate the functional role of LncRNA FENDRR in atherosclerosis that attenuates cell proliferation and accelerates cell apoptosis.