According to Moore's Law, as the feature size of semiconductor devices becoming smaller and smaller, the chip integration degree keeps increasing. In particular, accompanying with the development of high chip integration and unit size reduction, the metal interconnects, i. e. the wire bonding, are becoming a challenging problem. Copper wire is believed to be an excellent metal for wire bonding, instead of gold wire, due to its attractive advantages such as low cost, favorable electrical and thermal conductivities etc. However, the excess Cu/Al intermetallic compounds (IMC) at the interface of copper wire and aluminum pad will increase the contact resistance and reduce bonding strength. This can affect the properties and reliability of devices. Currently, the evolutions of the interfacial microstructures as well as the growth mechanism of Cu/Al IMC at the bonding interface under thermal condition are still unclear.In-situ transmission electron microscope (TEM) has high spatial resolution and strong analysis ability. With fast CCD cameras, TEM can also record the dynamic structure evolution of the sample in real time. Combined with multi-function holders, TEM can also exert diverse fields and loads on the sample and synchronously monitor their structures and component evolutions. Hence, in situ TEM provides an advanced technique to explore the structural evolution and growth mechanism of Cu/Al IMC.In this paper, the growth mechanism of Cu/Al IMC is investigated during the annealing temperature from 50-220 ℃ based on the in-situ high resolution transmission electron microscopy (in-situ HRTEM). Specifically, the dynamic growth and structural evolution of Cu/Al IMC during annealing are recorded in real time. Results show that the isolated Cu/Al IMC is distributed in the bonding interface before annealing. The main component of IMC is Cu9Al4, whereas the minor one of IMC is CuAl2. After annealing at 50-220 ℃ for 24 h, Cu/Al IMC near the Cu layer is Cu9Al4, while Cu-Al IMC apart from the Cu layer is CuAl2. Meanwhile, the reaction rates and the activation energy of Cu/Al IMC at different temperatures are calculated. Furthermore, the more accurate growth equation of Cu/Al IMC is also proposed based on the in-situ experimental results, which will benefit the optimization of bonding process and the reliability of Cu/Al wire bonding.