Objective To investigate correlation between nosocomial infection and the characteristics of agranulocytosis patients after chemotherapy to hematological malignancy, and to explore the risk factors. Methods By means of the retrospective study, the clinical and laboratory parameters of 214 agranulocytosis patients between July 2012 and June 2013 were analyzed. Among them, 68 without any infection were selected as group A; 84 with clinical diagnosis nosocomial infection, group B; and the rest 62 with etiology diagnosis nosocomial infection, group C. The data were analyzed with iterative multinomial logistic regression model after single factor analysis. Results The incidence of nosocomial infection was 68.22%. The results showed that acute myeloid leukemia (AML), seasons of hospitalization, WBC<0.8×10⁹/L, and no prophylactic antibiotics before infection were independent risk factors of nosocomial infection. Conclusion The incidence of nosocomial infection in agranulocytosis patients after chemotherapy to hematological malignancy is high. In order to improve treatment and prolong survival periods of these patients, good efforts should be taken on to prevent nosocomial infection. Prophylactic antibiotics may reduce the incidence of nosocomial infection, especially for the patients with AML, admitted in summer or autumn, or WBC<0.8×10⁹/L.