This study systematically investigated the electrochemical corrosion and static immersion corrosion behavior of the novel Ti6422 (Ti-6Al-4V-2Mo-2Fe) alloy with equiaxed (EM) and lamellar structure (LM) in HCl solution. The differences in corrosion performance between EM and LM samples were analyzed based on the characteristics of the passive film and substrate microstructure. Results indicated that the LM sample contained higher contents of TiO₂, Al₂O₃, and MoO₃ with higher stability compared with the EM sample, and the thickness of passive film was approximately twice that of the EM sample. Additionally, the donor density of LM sample was lower than EM sample. These findings indicate that the passive film on LM samples is thicker, with fewer defects and higher density. Electrochemical corrosion results revealed that the corrosion current of LM samples was lower and the polarization resistance was higher than these of EM samples, both suggesting superior corrosion resistance of LM samples. Immersion corrosion further confirmed that the LM sample had a lower corrosion rate. The enhanced corrosion resistance in LM samples was primarily due to higher content of corrosion-resistant β phase. Conversely, the numerous micro-galvanic cells between αs precipitates and adjacent β phase in EM samples weakened the corrosion resistance. Overall, these results demonstrated that regulating microstructure through heat treatment is an effective strategy for improving corrosion resistance of titanium alloys.