Objectives To analyze the risk factors of secondary infections in breast cancer or lung cancer patients with chemotherapy-induced degree Ⅳ neutropenia, so as to provide reference for clinical treatment. Methods The case-control study design was used. Thirty-seven in-patients of breast cancer or lung cancer with secondary infections and 87 in-patients without secondary infection in the First Affiliated Hospital of Xi’an Jiaotong University from January to December 2014 were enrolled as study population. We collected the retrospective information and analyzed the risk factors of secondary infection with chemotherapy-induced degree Ⅳ neutropenia using factors under univariate analysis and logistic regression analysis. Results Single factor analysis showed that the patients whose MASCC<21 the had higher infection risks (P<0.05). For breast cancer patients with degree Ⅳ neutropenia, secondary infection risk of first two chemotherapy cycles was 2.87 times of subsequent cycles of chemotherapy. For lung cancer patients with degree Ⅳ neutropenia, invasive procedures and preventive use of antibiotics increased risk of infection (P<0.05). Logistic regression analysis showed MASCC score and chemotherapy cycles were significantly associated with secondary infection in breast cancer degree Ⅳ neutropenia patients (P<0.05). Invasive procedures were significantly correlated to secondary infection of patients with lung cancer degree Ⅳ neutropenia (P<0.05). Conclusions MASCC score and chemotherapy cycles are the risk factors of infection in breast cancer patients with degree Ⅳ neutropenia, and invasive procedures are the independent risk factors of infection in lung cancer patients with degree Ⅳ neutropenia.