Assessment of individual responses of cells, tissues and the whole body to radiation exposure is an important challenge for radiobiology and radiation safety. The study was aimed to develop the method for estimation of the human hematopietic stem cell (HSC) individual response in the humanized mouse model. The cord blood or peripheral blood HSCs were administered to the NOD SCID immunodeficient mice. The number of maturing HSCs (CD34⁺ cells) and mature CD45⁺ leukocytes was assesed after the acute gamma exposure to the doses of 0.5 Gy, 1 Gy, and 1.5 Gy, along with the HSC share among all CD45^low/+ cells within three days (period of maximum mortality) and 14 days (period of active restoration) after exposure. The relationship between the indicato values and the exposure dose was calculated by regression analysis. There was exponential relationship between the human HSC survival rate in humanized mice and the dose on day three after exposure (R² = 0.93; F = 211; p < 0.01), while the relationship between the number of HSCs and the dose on day 14 after exposure was linear (R² = 0.65; F = 12.9; p = 0.01). The C14/3 coefficient calculated as a ratio of the HSC share among all human CD45^low/+ cells on day 14 after exposure to the same parameter on day three after exposure was proposed as an indicator of HSC mortality and HSC number restoration. C14/3 negatively correlated with the exposure dose (R² = 0.57; F = 13.3; p = 0.004), it was higher in radioresistant mice and the model of  cysteamine-induced radioresistance in humanized mice. The model mice humanized using the peripheral blood HSCs can be used to assess individual HSC response to acute external gamma exposure based on C14/3 and the data on the HSC survival and restoration.