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The high incidence of premature rupture of membranes (PROM) is closely related to the lack of screening methods. Herein, a rapid and sensitive detection model for procalcitonin (PCT) and interleukin-6 (IL-6) was established utilizing the principle of antigen antibody binding and combined with surface enhanced Raman spectroscopy (SERS) and immunochromatographic assay (ICA), which could be used for the detection of specific biomarkers at a low concentration of peripheral blood and early detection of PROM patients. 5,5′-Dithiobis-2-nitrobenzoic acid labeled monoclonal anti-IL-6 on gold nanocages (GNCs) and 4-methylthiobenzoic acid labeled monoclonal anti-PCT on GNCs were employed as SERS tags. In the presence of IL-6 and PCT, the antigen-SERS tag complexes were trapped and concentrated on the two test lines. The unique characteristics of GNCs with hollow and multi-branch angle allowed high SERS performance in the system by increasing the biological binding sites and hot spots. Through finite difference time domain simulation, it could be concluded that the electromagnetic field between the gaps of GNC dimers was stronger than that of the single GNC, which proved the feasibility of ICA based on surface enhanced Raman scattering (SERS-ICA) in theory. The detection limits of IL-6 and PCT in phosphate buffer were 7.897 pg mL−1 and 7.725 pg mL−1, meanwhile the detection limits of peripheral blood were 8.414 pg mL−1 and 8.017 pg mL−1, respectively. In addition, the detection of real-world samples showed that SERS-ICA was available to evaluate the concentrations of IL-6 and PCT. The experimental data of SERS-ICA were in accordance with that of enzyme-linked immunosorbent assay. These results indicated that SERS-ICA had great potential in the early screening of PROM. [ABSTRACT FROM AUTHOR]