This paper focuses on seru scheduling problems considering the sequence-dependent setup time in seru production system (SPS), which is a new-type manufacturing system originated in Japanese production practice recently that can better adapt to the fluctuate market demand. A mixed integer programming (MIP) model with the objective of minimizing the sum of the makespan and the weighted tardiness is constructed for the seru scheduling problem. The two-phase B&B (TPBB) algorithm is designed subsequently, where the first phase solves the assignment of products to serus , while the second phase solves the scheduling optimization in each seru . Finally, the computational experiments and comparative analysis with CPLEX 12.8 are made, and the report of results verifies that the effectiveness and practicability of the proposed MIP model and TPBB algorithm.