Obesity is a serious worldwide disease, which is growing in epidemic proportions. Adipose-derived stem cells (ADSCs) are characterized as a source of mesenchymal stem cells that have acted as a potential application for regeneration. Recently, seaweeds rich in flavonoids and polysaccharides have been supposed to show the ability to modulate risk factors for obesity and related diseases. In the present study, we investigated the anti-obesity properties of high stability fucoxanthin (HS-Fx) derived from brown seaweeds on the adipogenesis of ADSCs upon treatment with palmitic acid (PA). First, we showed the differentiation capability of ADSCs from morbid obesity patients to transform into different cell types. Second, we found that the co-treatment of ADSCs with HS-Fx and PA showed no significant cytotoxicity against ADSCs, but PA induced the elevation of reactive oxygen species (ROS) and lipid droplet accumulation was abolished. Thirdly, the PA-mediated down-regulation of lipid metabolism genes was reversed by the treatment of HS-Fx. By long non-coding RNAs (lncRNAs) screening, we found that PA-induced increases in the targeted lncRNAs were also decreased upon treatment with HS-Fx. On Silencing, these lncRNAs corresponded to the decrease in the lipid droplet accumulation of ADSCs induced by PA. ADSCs from obese patients would be direct and meaningful model cells to investigate the development of obesity-related diseases and their treatments, rather than cell lines from other species. HS-Fx showed anti-obesity capability through modulating the elevation of ROS, down-regulation of lipid metabolism genes induced by PA, and upstream signaling, which might be critically resulted from the expression of lncRNAs.