Noble metals such as gold and silver play important role in the fabrication of SERS substrates, however, the high cost of noble metals has become an obstacle when SERS start to move out of the research laboratory and into practice. Recently, self-cleaning substrates have drawn more and more attention due to their recyclable ability and further reducing cost. In this work, a flower-like Au@MoS2/Ag NPs nanocomposite with core-shell structure was synthesized by hydrothermal method. The employment of MoS2 endows the substrate with a high adsorption capacity and photocatalytic ability. Finally, a highly sensitive, self-cleaning, and recyclable SERS substrate was constructed by combining the synergistic effect of noble metal nanoparticles (Au, Ag) and the photocatalytic ability of MoS2. Methylene blue (MB) was used to evaluate the SERS performances of the as-prepared substrate, and the results show that the as-prepared substrate has good signal uniformity with relative standard deviation (RSD) of 8.2 %, and good batch-to-batch stability with the RSDs of 4.9 %, 5.7 %, and 5.3 % at 1625 cm−1, 1401 cm−1, and 451 cm−1, respectively. In the range of 10−5–10−10 M, the concentration of the analyte showed a good linear relationship with the Raman peak intensity at 1625 cm−1, with the correlation coefficient R2 of 0.9821, and the detection limit was 8.9 × 10−11 M. In addition, the photocatalytic performance of the substrate was investigated, 97.1 % of the MB was degraded under the irradiation of the Xe lamp for 100 min, and the SERS signal remained at 62.8 % of the initial signal after 8 cycles. The flower-like Au@MoS2/Ag NPs self-cleaning SERS substrate developed in this work shows good renewable performance and is expected to be used as a new SERS substrate in food, medicine, environmental, and other analytical fields.