In order to determine the effect of Sb element on the welding reliability of Sn-Sb alloy solder, the interfacial behavior of Sn-Sb alloys with different Sb contents on the Cu substrate was investigated. The evolution process of interfacial layers was explained by analyzing the microstructure and interfacial reaction thermodynamics of Sn-xSb/Cu system. The addition of Sb has a non-monotonic effect on the intermetallic compound layers. Sb can inhibit the diffusion of Cu into solder. The addition of 3 wt.% Sb in the alloy reduces the activation energy of interfacial reaction from 286.41 to 62 kJ/mol, which promotes the interfacial reaction. The addition of 10 wt.% Sb increases the activation energy of interfacial reaction to 686.73 kJ/mol, which inhibits the interfacial reaction and reduces the erosion of the Cu substrate by the solder and inhibits the formation of an excessively thick interfacial layer.