Laser cladding is a new technology for fabricating coatings with good properties, such as wear resistance, lubrication, and corrosion resistance. Usually, parts of 45 steel are used as a shaft under conditions of high-speed rotation or friction and wear, and they have a short service life and sometimes cause accidents. In order to avoid serious accidents, a cladding coating made from a Ni-based alloy with ceramic particles was fabricated via laser technology on a substrate of 45 steel in this research. The microstructure and properties were investigated via SEM, EDS, XRD, and a wear and friction tester. The results show that there was an obvious boundary between the cladding coating and the substrate. The main phases were γ(Fe, Ni), WC, TiC, Cr2Ti, and Cr23C6. In the middle of cladding coating, the microstructure was composed of dendrite and cellular crystals, while the microstructure was composed of equiaxial crystals in the bonding region. Inside the cellular crystal, the main phase was γ~(Fe, Ni), which occasionally also showed the appearance of some white particles inside the cellular crystal. Compared with the cellular crystal, the boundary had less of the Fe and Ni elements and more of the Cr and W elements. The amount of C element around the dendrite crystal was more than that around the boundary of cellular crystal due to the long formation time of dendrite. The white particles around the boundary were carbides, such as WC and Cr23C6 phases. Meanwhile, the segregation of the Si element also appeared around the boundaries of the crystal. The maximum microhardness was 772.4 HV0.5, which was about 3.9 times as much as the substrate’s microhardness. The friction coefficients of the 45 steel substrate and Ni-based alloy coating were usually around 0.3 and 0.1, respectively. The Ni-based coating had a smaller coefficient and more stable fluctuations. The wear volume of the cladding coating (0.16 mm3) was less than that of the substrate (1.1 mm3), which was about 14.5% of the wear volume of 45 steel substrate. The main reason was the existence of reinforced phases, such as γ~(Fe, Ni), Cr23C6, and Cr2Ti. The added small WC and TiC particles also enhanced the wear resistance further. The main wear mechanism of the cladding coating was changed to be adhesive wear due to the ceramic particles, which was helpful in improving the service life of 45 steel.