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Background Hemorrhagic fever with renal syndrome (HFRS) is an endemic disease occurring in various parts of the world. Prompt access to care with proper treatment is essential for preventing patients from developing renal failure and unfavorite outcomes. This study aimed to elucidate laboratory parameters associated with HFRS severity and prognosis to predict disease course and initiate prompt clinical management. Methods Retrospective analysis of laboratory data was performed on HFRS patients from December 2016 to January 2022 in Baoji City of Shaanxi Province in China using different statistical methods. Results The WBC and neutrophils in peripheral blood, RBC in urine sediments, blood, protein, and glucose in urine, PT/INR, aPTT, TT, AST, ALT, AST/ALT, MAO, AD, urea, creatinine, cystatin C, CK‐MB, LDH, α‐HBDH, mAST, triglycerides, glucose, amylase, ferritin, and PCT in serum increased in HFRS patients along with disease severity, while the lymphocytes, monocytes, platelets, plateletcrit, fibrinogen, serum total protein, albumin, HDL‐c, magnesium, complement C3 and C4, IgG, triiodothyronine, thyroxine, and free triiodothyronine were reduced. Results also indicated that in uncured HFRS patients, the NEUT%, CRP, cast, PT/INR, aPTT, D‐dimer, AST/ALT, CK‐MB, LDH, α‐HBDH, m‐AST, ferritin, and PCT were significantly higher than in cured patients, while platelets, C3, and C4 in uncured patients were significantly lower than in cured patients. The NEUT%, CRP, AST/ALT, and LDH were associated with patients' prognosis. Conclusions Laboratory data are helpful in predicting HFRS patients' progress, severity, and prognosis, thus, these parameters are useful in guiding prompt clinical management of patients. Prompt access to care with proper treatment is essential for preventing patients from developing renal failure and unfavorable outcomes. This study aimed to elucidate laboratory parameters associated with HFRS severity and prognosis to predict disease course and initiate prompt clinical management. Retrospective analysis of laboratory data was performed on HFRS patients from December 2016 to January 2022 in Baoji City of Shaanxi Province in China using different statistical methods. Multiple abnormal laboratory results were found in patients with HFRS when compared with healthy subjects. The WBC and neutrophils in peripheral blood, RBC in urine sediments, blood, protein, and glucose in urine, PT/INR, aPTT, TT, AST, ALT, AST/ALT, MAO, AD, urea, creatinine, cystatin C, CK‐MB, LDH, α‐HBDH, mAST, triglycerides, glucose, amylase, ferritin, and PCT in serum increased along with disease severity, while the lymphocytes, monocytes, platelets, plateletcrit, fibrinogen, serum total protein, albumin, HDL‐c, magnesium, complement C3 and C4, IgG, triiodothyronine, thyroxine, and free triiodothyronine were reduced. Results also indicated that in uncured HFRS patients, the NEUT%, CRP, cast, PT/INR, aPTT, D‐dimer, AST/ALT, CK‐MB, LDH, α‐HBDH, m‐AST, ferritin, and PCT were significantly higher than in cured patients, while platelets, C3, and C4 in uncured patients were significantly lower than in cured patients. The NEUT%, CRP, AST/ALT, and LDH were associated with patients' prognosis. Laboratory data are helpful in predicting HFRS patients' progress, severity, and prognosis; thus, these parameters are useful in guiding prompt clinical management of patients.