Abstract: Objective To identify biomarkers which can be used of estimating the biological behaviors of prostate cancer with osseous metastasis. Methods Collecting the sera of prostate cancer patients with and without osseous metastasis, and pooling the two group of serum respectively. Using two-dimensional gel electrophoresis (2-DE) followed by capillary liquid chromatography（Cap LC）and tandem mass spectrometry（MS/MS） to detect the differential serum proteins between prostate cancer patients with and without osseous metastasis. Enzyme linked immunosorbent assay (ELISA) was used to validate differential serum proteins. Results Serum amyloid A (SAA) and cytokeratin 10 (CK10) were higher expression level in prostate cancer patients with osseous metastasis, while apolipoprotein A-Ⅰ(ApoA-Ⅰ) was determined to be down-regulated in this group. And the expression level of ApoA-Ⅰ was confirmed by ELISA analysis. Conclusion Our experiment indicated that the expression level of serum protein ApoA-Ⅰ, SAA and CK10 was correlated to the osseous metastasis of prostate cancer.