The current study aimed to analyze the clinical characteristics of severe fever with thrombocytopenia syndrome (SFTS) and to explore the risk factors of critical patients. From 2016 to 2018, we collected the hospitalized diagnosed cases with SFTS in Jinan infectious disease hospital of Shandong University and analyzed by the descriptive epidemiological method. According to the prognosis, they were divided into general group and severe group. The epidemiological characteristics, clinical features, and laboratory indexes of these 2 groups of patients were compared and analyzed at the first visit. The risk factors related to the severity of the disease were analyzed by univariate Logistic regression. In total, 189 cases of SFTS were treated during the period and 33 deaths occurred in the severe group, with the fatality rate of 17.46%. The patients' age (χ = 8.864, P < .01), ALT (Z = -2.304, P = .03), AST (Z = -3.361, P < .01), GLU (t = -4.115, P < .01), CK (Z = -3.964, P < .01), CK-MB (Z = -2.225, P = .03), LDH (Z = -3.655, P < .01), α-HBDH (Z = -2.040, P = .04), APTT (t = -3.355, P < .01), BUN (Z = -2.040, P = .04), Cr (Z = -3.071, P = .01), and D-dimer (Z = -2.026, P = .04) in the severe group were higher than that in the normal group, but the blood platelet (PLT) counts were significantly lower (Z = -2.778, P < .01) than that in the normal group. With the neuropsychiatric symptoms (OR = 24.083, 95% CI = 6.064-95.642), skin bleeding point (OR = 30.000, 95% CI = 6.936-129.764), multiple organ dysfunction (OR = 34.048, 95% CI = 7.740-149.782), past medical history (OR = 3.792, 95% CI = 1.284-11.200), and fasting glucose elevation (OR = 1.359, 95% CI = 1.106-1.668) could predict the severity of the SFTS. In summary, the abnormality of the laboratory index, the special clinical manifestations, and the past medical history of SFTS patients were the important basis for judging the patient's serious condition.