The use of polyols obtained from natural renewable sources for the synthesis of thermoplastic polyurethanes (TPU) is widely known and the industry has moved toward the replacement of petrochemical content, allowing the production of biobased TPU devices in large scale. The use of nanoparticles (NP) to improve specific properties of polymeric materials has been extensively studied and in general, the achieved reinforcement effect is dependent on the NP intrinsic characteristics (aspect ratio, shape, surface area, rigidity), on a proper NP’s dispersion and distribution through the polymeric matrix and on the compatibility/affinity between the components. Halloysite nanotubes (HNT) have been used as reinforcing NPs because they have interesting characteristics: aspect ratio and shape similar to the carbon nanotubes and a chemical structure analogous to the montmorillonite. In this work, the influence of the processing conditions on mechanical properties of biobased TPU/HNT nanocomposites was evaluated. The melt mixing was done in an internal mixer (Haake Rheomix OS, 80 rpm, 10 min of mixture); two processing routes were used, the direct mixing (1 step process) and the masterbatch/dilution approach (2 steps process), in two temperatures (150 and 180°C), producing 5 wt% HNT loading samples. Transmission electron microscopy (TEM) analyses indicate that the HNT distribution and dispersion are dependent of the processing conditions applied: the 2 steps process produced well dispersed nanocomposites and the dilution at 180°C also improved the HNT distribution through the TPU. As consequence, the highest reinforcement effect was achieved, with a 40% increase in the elastic modulus (with insignificant loss in elongation at break).