Aiming at the problem of shipping schedule design of container liner transportation under the imbalance of cargo flow, according to the functional relationship between fuel consumption, vessel speed and cargo weight in each segment, and combined with the collaborative agreement of vessel arrival multi time window, multi departure, arrival time and multi handling efficiency, a nonlinear programming model for liner transportation vessel schedule design was constructed to optimize the speed of each segment, and the linear secant approximation method was designed to solve the model. Taking the AWE1 route served by CHINA COSCO SHIPPING GROUP as an example, the values of 100 scenarios were generated for simulation calculation. The results show that the optimization of vessel scheduling considering imbalance cargo flow can effectively reduce the total roundvoyage cost of container liner shipping, which  conduct to increasing the shipping capacity. The sensitivity analysis results show that the proposed model is beneficial to slow down the rapid increase of total liner voyage cost caused by the increase of fuel price, and larger the cargo flow imbalance coefficient, more effective the model. The conclusion can provide useful reference for vessel scheduling decision of shipping companies.