Objective:To investigate the diagnostic value of serum proliferating cell nuclear antigen (PCNA), tissue metalloproteinase inhibitor-1 (TIMP-1) levels combined with single photon emission computed tomography (SPECT) in lung cancer bone metastasis.Methods:82 patients with bone metastasis of primary lung cancer (observation group) and 82 patients without bone metastasis (control group) in Kashgar Prefecture Second People's Hospital from February 2017 to August 2019 were retrospectively analyzed. The levels of PCNA and TIMP-1 in serum were detected by enzyme-linked immunosorbent assay (ELISA); bone metastasis were detected by SPECT; Pearson method was used to analyze the correlation between serum PCNA, TIMP-1 levels and SPECT bone imaging grade; The diagnostic value of SPECT and serum levels of PCNA and TIMP-1 in bone metastasis of lung cancer was analyzed by drawing the receiver operating characteristic curve; the diagnostic value of SPECT combined with serum levels of PCNA and TIMP-1 in bone metastasis of lung cancer was analyzed by four grid table with magnetic resonance imaging (MRI) as the gold standard.Results:Compared with the control group, the serum levels of PCNA and TIMP-1 in the observation group were significantly higher ( P<0.05), and increased with the increase of the extend of disease (EOD) grade ( P<0.05). The AUC of serum PCNA and TIMP-1 levels in the diagnosis of bone metastasis of lung cancer were 0.835 (95% CI: 0.771-0.898) and 0.814 (95% CI: 0.746-0.882), respectively. When cutoff values were 388.76 pg/ml and 524.45 pg/ml, the sensitivity were 82.70%, 79.00%, and the specificity were 74.40%, 76.80%, respectively. The sensitivity and specificity of SPECT were 82.93% and 90.24% respectively. The sensitivity and specificity of serum PCNA, TIMP-1 levels combined with SPECT in the diagnosis of bone metastasis of lung cancer were 95.12% and 91.46%, respectively, which were higher than those of serum PCNA, TIMP-1 levels and SPECT alone. Conclusions:Increased serum PCNA and TIMP-1 levels are related to bone metastasis of lung cancer and its severity. Combined SPECT and serum PCNA, TIMP-1 detection is of high diagnostic value for bone metastasis of lung cancer.