In our study, we found that USP3 interacted with Aurora A to reduce the ubiquitination level of Aurora A and inhibited the proteasome degradation pathway of Aurora A. We constructed the deubiquitinated mimetic K143R of Aurora A and found that K143R significantly promoted the proliferation and invasion of ESCC cells, and was not regulated by the deubiquitination of USP3. Here, USP3 is linked to esophageal squamous cell carcinoma.