Background Pneumocystis jiroveci pneumonia (PJP) is the most common opportunistic infection in immunocompromised patients. The accurate prediction of PJP development in patients undergoing immunosuppressive therapy remains challenge. Methods Patients undergoing immunosuppressive treatment and with confirmed pneumocystis jiroveci infection were enrolled. Another group of matched patients with immunosuppressant treatment but without signs of infectious diseases were enrolled to control group. Results A total of 80 (40 PJP, 40 non-PJP) participants were enrolled from Tongji Hospital. None of the patients were HIV positive. The routine laboratory indicators, such as LYM, MON, RBC, TP, and ALB, were significantly lower in PJP patients than in non-PJP patients. Conversely, LDH in PJP patients was significantly higher than in non-PJP controls. For immunological indicators, the numbers of T, B, and NK cells were all remarkably lower in PJP patients than in non-PJP controls, whereas the functional markers such as HLA-DR, CD45RO and CD28 expressed on CD4(+) or CD8(+) T cells had no statistical difference between these two groups. Cluster analysis showing that decrease of host immunity markers including CD3(+), CD4(+) and CD8(+) T cells, and increase of tissue damage marker LDH were the most typical characteristics of PJP patients. A further established model based on combination of CD8(+) T cells and LDH showed prominent value in distinguishing PJP from non-PJP, with AUC of 0.941 (95% CI, 0.892-0.990). Conclusions A model based on combination of routine laboratory and immunological indicators shows prominent value for predicting the development of PJP in HIV-negative patients undergoing immunosuppressive therapy.