Atherosclerosis is a chronic progressive inflammatory vascular disease. The dysfunction of vascular smooth muscle cells (VSMCs) induced by oxidized low-density lipoprotein (ox-LDL) contributes to the formation of atherosclerotic lesions. Additionally, upregulation of the long non-coding RNA zinc finger antisense 1 (ZFAS1) was observed in the plaques of patients with atherosclerosis. The aim of the present study was to explore the functional role of ZFAS1 in atherosclerosis progression. Reverse transcription-quantitative PCR was performed to analyze ZFAS1 mRNA expression, and western blotting was performed to determine the protein expression levels of Ki67, proliferating cell nuclear antigen (PCNA), matrix metallopeptidase (MMP)2 and MMP9. The Cell Counting Kit-8 assay was used to test cell viability. Finally, wound healing and Transwell chamber assays were performed to evaluate cell migration and invasion, respectively. The current findings demonstrated that ZFAS1 expression was upregulated by ox-LDL stimulation in VSMCs. Moreover, ZFAS1 overexpression promoted the ox-LDL-induced proliferation, migration and invasion of VSMCs, and upregulated the expression levels of proteins associated with cellular proliferation (Ki67 and PCNA), migration and invasion (MMP2 and 9). By contrast, ZFAS1-knockdown inhibited the proliferation, migration and invasion of VSMCs, and suppressed cell proliferation-, migration-and invasion-associated protein expression. In conclusion, ZFAS1 promoted the ox-LDL-induced proliferation, invasion and migration of VSMCs. Thus, ZFAS1 may represent a novel biomarker for dysfunction of VSMCs in the pathological condition of atherosclerosis.