The novel Fe-based alloy with high wear resistance, corrosion resistance and self-lubricating properties has significant application prospects in the field of remanufacturing key components in metallurgical equipment. However, problems still exist in the alloy composition design, process and microstructure performance control. In this paper, the material genome design method was adopted to design and study a new alloy powder composition that simultaneously possesses three genetic phases of wear resistance, corrosion resistance and self-lubrication by adding S element to Fe-Cr-Ni system alloy. The laser cladding process was utilized to fabricate the novel Fe-based alloy samples with the integrated properties. The results demonstrate that a material genome design method for multi-element alloy with three genetic phases of wear resistance, corrosion resistance and self-lubrication were successfully constructed. The fabricated Fe-based alloy sample exhibited better laser formability as well as high wear resistance, corrosion resistance, and self-lubrication, and the matched three-phase structure consists of martensite and Cr23C6 carbide as the wear-resistant genetic phase, austenite and a chromium-rich passive film as the corrosion-resistant genetic phase, and a in situ formed 2.27 wt% CrS self-lubricating genetic phase. The study reveals that the synergistic effect of Cr element in the three genetic phases contributed to the formation of enhanced wear-resistant, corrosion-resistant, and self-lubricating genetic structure phases. This work provides a useful reference for laser cladding parts with high wear and corrosion resistance and self-lubricating performance.