The development of human–computer interfaces in different individuals occur with different efficiencies, this is due to the individual characteristics of the genotype determined by the single-nucleotide polymorphism (SNP) of a person. Here, we checked the connection between the success of the acquisition of the brain-computer, eye-tracking, electromyographic, and respiratory interfaces and SNP of the TOMM40, BDNF, HTR2A and TPH2 genes. Here, we show that the T-allele in rs6313 of the HTR2A gene is associated with an increase in the number of correctly submitted commands of the electromyographic and eye-tracking interfaces. This is probably due to the fact that, the T-allele carriers decrease expression of this serotonin receptor. The decreased expression of HTR2A may be a reason for an increase in the number of accurately submitted commands. It was shown that the TT genotype of rs4290270 polymorphism was associated with an increase in the accuracy of work with the myographic interface. In addition, the association of subjective interfaces work time with polymorphisms rs429358 and rs2030324 was noted. Thus, the genotypic characteristics of individuals can be a predictive sign for the degree of success of mastering human–computer interfaces, which can allow to expand the understanding of training the neural mechanisms when working with this class of devices.