Fixture layout is an essential factor in intelligent manufacturing in the shipbuilding industry, affecting assembly quality and efficiency. Its optimization has become an urgent problem in the assembly process of compliant parts. Traditional fixture layout depends on workers’ experience, which leads to butt clearance along the assembly interface. This article proposes a butt clearance control-oriented fixture layout optimization (BCCFLO) methodology. First, a method for calculating the part dimensional variation under the influence of fixture layout and fixture locating error is developed. Then, a constrained multi-objective integer nonlinear programming (CMINP) model is formulated to optimize the fixture layout. Furthermore, a non-dominated sorting genetic algorithm II based on Latin hypercube sampling is designed to address the CMINP model. The case study validates that the fixture layout achieved by the proposed method significantly controls the butt clearance for large compliant part assembly in the shipbuilding industry.