Silicon is considered one of the most promising anode materials owing to its high theoretical energy density, however, the volume expansion/contraction during electrochemical lithiation/delithiation cycles leads to instability of the solid electrolyte interphase (SEI), which ultimately results in capacity degradation. Herein, the local stress and deformation evolution status of an SEI layer on an anode particle are investigated through a quantitative electrochemical-mechanical model. The impacts of structural uniformity, mechanical strength, and operating conditions on the stability of the SEI layer are investigated in detail. The simulation results demonstrate that when the silicon particle radius decreases from 800 nm to 600 and 400 nm, the failure time increases by 29% and 65%, respectively, of the original failure time; When the structural defect depth ratio is reduced from 0.6 to 0.4 and 0.2, the failure time increases by 72% and 132%, respectively; For the discharge rate, the condition at 0.1 C has 34% and 139% longer time to failure than that at 0.2 C and 0.3 C, respectively. This work provides insight into the rational design of stable SEI layers and sheds light on possible methods for constructing silicon-based lithium-ion batteries with longer cycling lives.