A process intensification study for the full hydrogenation of bio-derived platform molecule squalene (SQE) into squalane (SQA), using commercial heterogeneous Pd catalysts and Pd supported on carbon nanotubes (CNT) is reported. Pd/CNT shows a substantial improvement of the catalytic activity for the total hydrogenation of SQE into SQA thanks to cooperativities between Pd nanoparticles and single atoms simultaneously present on the CNT. However, the stirred reactor's productivity, scalability, and operability are limited by the exothermicity of the reaction (ΔrH = − 765 kJ.mol−1). The implementation of the Pd/CNT catalyst in flow was then studied after coating this catalyst on metallic open cell foams. Using the foam-based milli-reactor's characteristics, including high mass and heat transfer rates and safety, fully reduced SQA (>99 %) was obtained at 180 °C and 30 bar of H2 for a contact time of 1.45 min with a space–time yield of 68 molSQA.molPd−1.min−1. Finally, a scale-up strategy (7 fold) was successfully attempted in a commercially available pilot-scale reactor that meets further seamless scale-up requirements. A production capacity of 2 kg per day using a commercial intensified reactor with a reacting volume of 43.2 mL was obtained under mild conditions (120 °C and 30 bar of H2).