The liver plays a key role in the metabolism of lipoproteins, controlling both productionand catabolism. To accelerate the development of new lipid-lowering therapies inhumans, it is essential to have a relevant in vitro study model available. The currenthepatocyte-like cells (HLCs) models derived from hiPSC can be used to model manygenetically driven diseases but require further improvement to better recapitulate thecomplexity of liver functions. Here, we aimed to improve the maturation of HLCs usinga three-dimensional (3D) approach using Biomimesys®, a hyaluronic acid-based hydro-scaffold in which hiPSCs may directly form aggregates and differentiate toward a func-tional liver organoid model. After a 28-day differentiation 3D protocol, we showedthat many hepatic genes were upregulated in the 3D model (liver organoids) in compar-ison with the 2D model (HLCs). Liver organoids, grown on Biomimesys®, exhibited anautonomous cell organization, were composed of different cell types and displayedenhanced cytochromes P450 activities compared to HLCs. Regarding the functionalcapacities of these organoids, we showed that they were able to accumulate lipids(hepatic steatosis), internalize low-density lipoprotein and secrete apolipoproteinB. Interestingly, we showed for the first time that this model was also able to produceapolipoprotein (a), the apolipoprotein (a) specific of Lp(a). This innovative hiPSC-derived liver organoid model may serve as a relevant model for studying human lipopo-protein metabolism, including Lp(a).KEYWORDScytochrome activities, hiPSC-derived liver organoids, hyaluronic-acid based hydroscaffold, lipidmetabolism, liver steatosis, Lp(a)