Xinjiang represents one of the richest minorities’ areas in China. This high ethnic diversity reflects in the blood groups and immune status and has a consequent impact on blood transfusions. To evaluate the risks of cross-minority transfusion in Xinjiang, we investigated the frequencies of erythrocytic Rh and K antigens among 1,073 Uyghurs and 213 Kazaks. We further reviewed the literature on the frequency of erythrocytic antigens to develop a simulation model for calculating the risk of patients in Xinjiang exposed to mismatched erythrocytic antigens. The frequencies of RhE, RhC, and K phenotypes were as follows: C antigen, 52.3% in Uyghurs and 56.8% in Kazaks; c antigen, 47.7% in Uyghurs and 43.2% in Kazaks; E antigen, 25.5% in Uyghurs and 27.2% in Kazaks; e antigen, 74.5% in Uyghurs and 72.8% in Kazaks; K antigen, 1.8% in Uyghurs and 1.8% in Kazaks. The population-adjusted cumulative match rate demonstrated that 53.3%, 51.4%, 50.6%, and 53.7% of the Uyghur, Kazak, Han, and Hui populations were recipients, respectively, although the recipients were transfused with an unknown Rh blood type. We concluded that the risks of cross-minority transfusion in Xinjiang are insignificant. The best strategy appears to be K and Rh-matched transfusions in this region due to the much higher frequency of the K antigen compared to other areas in China.