Objective To study the hardness properties of pig esophageal at the nanoscale using atomic force microscope (AFM). Methods The porcine esophagus was chosen as experimental sample to study the hardness properties of esophageal tissues at different loading rates, deflection and dwell time with AFM. Results The hardness of esophageal tissues at the nanoscale was strongly correlated with the loading rate and the deflection, which increased with the increasing loading rate and decreased with the increasing deflection of cantilever. The difference in the hardness was associated with the viscoelasticity and viscoplasticity of esophageal tissues, including contact stress, energy transition and strain plastic gradient. Conclusions The experimental results have important significance for clinical diagnosis, surgical operation and artificial material development, and reveal the changing patterns for mechanical properties of the esophageal tissues at the microscale.