Ensartinib is a promising, aminopyridazine-based small molecule that potently inhibits anaplastic lymphoma kinase. This random, two-period, crossover study evaluated the effects of food on the pharmacokinetics of ensartinib after a single dose (225 mg) in healthy Chinese subjects. The pharmacokinetic parameters of ensartinib were calculated using non-compartmental analysis. Twenty-four Chinese healthy subjects aged 20–44 years were included in this study. The area under the concentration–time curve of ensartinib was approximately 25% lower after the intake of a high-fat, high-calorie meal prior to dosing, whereas the maximum plasma concentration was decreased by approximately 37%, illustrating the statistically significant effect of food on ensartinib pharmacokinetics. In addition, food intake prolonged the absorption phase of ensartinib (median time to maximum plasma concentration, from 4.5 to 6 h). Population pharmacokinetic (PopPK) analysis was conducted using NONMEM, and the influences of food, age, sex, body weight, and body mass index were studied via covariate analysis. In this analysis, ensartinib plasma concentrations were best described by a one-compartment model with Weibull absorption. The final model included food and age as covariates on apparent distribution and apparent clearance. Based on the final PopPK model, food was identified as a significant covariate for apparent clearance, apparent volume of distribution, and absorption rate constant, consistent with the results of non-compartmental pharmacokinetic analysis.