AA4045/AA3003 cladding billet was prepared by direct chill semi-continuous casting process. The macrostructures, microstructures, temperature distribution, compositions distribution and the mechanical properties at the bonding interface were investigated in detail. The results show that the cladding billet with few defects could be obtained by semi-continuous casting process. At the interface, diffusion layer of about 10μm on average formed between the two alloys due to the diffusion of alloy elements in the temperature range from 596 to 632 °C. From the side of AA4045 to the side of AA3003, the Si content has a trend to decrease, while the Mn content has a trend to increase gradually. Tensile strength of the cladding billet reaches 103.7 MPa, the fractured position is located on the AA3003 side, and the shearing strength is 91.1 MPa, revealing that the two alloys were combined metallurgically by mutual diffusion of alloy elements.