Objective To evaluate the diagnostic and predictive value of combined detection of sex hormone-bin-ding globulin (SHBG) and serum amyloid A4 (SAA4) in smear-negative pulmonary tuberculosis(SNPT). Methods Serum specimens of 88 SNPT patients who were admitted to Lontan Hospital, Liuzhou, Guangxi from March to May, 2017 were collected, serum specimens of 56 healthy physical examination people in Liuzhou City collected at the same time were as control group. Serum levels of SHBG and SAA4 in SNPT group and control group were measured by enzyme-linked immunosorbent assay (ELISA), efficacy of single and combined diagnosis for SNPT was compared by receiver operating characteristic(ROC) curve, and compared with the diagnostic efficacy of T cell spot test of tuberculosis infection (T-SPOT TB) for SNPT in recent three years. Results Concentrations of serum SHBG and SAA4 were 52.32 (24.58-81.19) nmol/L and 56.71 (41.87-77.57) ng/mL in SNPT group, 25.97 (16.60-36.45) nmol/L and 35.79 (29.81-41.07) ng/mL in control group, expression levels of serum SHBG and SAA4 in SNPT group were both significantly higher than those in control group (both P<0.001). The area under ROC curve of single and combined diagnosis of SNPT by SHBG and SAA4 were 0.781, 0.829, and 0.906, respectively (all P<0.001), sensitivity and specificity of the combined diagnosis were 84.1% and 91.1% respectively, Jordan index was 0.752. Compared with T-SPOT TB detection method reported in recent three years, combined detection of SHBG and SAA4 has advantage for the diagnosis of SNPT. Conclusion SHBG and SAA4 has good auxi-liary diagnostic value for SNPT, and the combined detection can improve the diagnosis rate of SNPT.