A microstructure-based homogenization model is proposed for simulating the cyclic plasticity and predicting the low-cycle fatigue (LCF) crack initiation life of GH4169 superalloy. Classical crystal plastic model (CPM) with a simple softening model is used at the grain level. Then, the transition from grain level to polycrystal level is based on the conservation of virtual work between the two levels. The Eshelby's formulation is applied in the model. Especially, local influences of grain interactions are considered by introducing the external Eshelby's tensor. Relatively precise macroresults and microresults as the finite element method can be provided by the present model with less computational cost. Grain volume averaged fatigue indicator parameters (FIPs) with considering the effect of inclusions are formed to predict the LCF crack initiation life, and a fold-line fitting model is proposed to substitute for the cycle-by-cycle simulation. Predicted lives fit well with the experimental data for both the strain loading and stress loading simulations. Scatter of the life can also be predicted by the model and overwhelming influences of the incubation stage on the variability of LCF initiation life can be captured. It is shown that the inclusions and the inhomogeneous plastic strain are responsible for the scatter of the incubation stage.