iPSC-derived medium spiny neurons (MSNs) is a cellular model to study neurodegeneration in Huntington’s disease. This model allows to study molecular mechanisms of the disease, large-scale drug screening, and toxicological studies. We generate MSNs from human PSCs using the protocol we created (Grigor’eva et al., 2020, doi: 10.1007/s10616-020-00406-7). The first stage involved dual-SMAD signalling inhibition through treatment with SB431542 and LDN193189 resulting in the generation of SOX1-, PAX6-, and OTX2-positive neuroectodermal cells. The next stage was the derivation of actively proliferating MSN progenitor cells. At the terminal stage MSNs expressed specific markers such as GABA and DARPP32.