Dynamic facility layout problems involve devising the optimal layout for each different production period. This article studies unequal-area dynamic facility layout problems under fuzzy random environment to minimize the sum of the material handling costs and rearrangement costs. For a more general situation, a novel model of unequal-area dynamic facility layout problems is proposed on the basis of fuzzy random theory, in which uncertain demands are characterized by fuzzy random variables. Unequal-area dynamic facility layout problems are one of the non-deterministic polynomial-time hard problems. Therefore, a hybrid particle swarm optimization and simulated annealing algorithm is innovated to solve the proposed unequal-area dynamic facility layout problems model under fuzzy random environment, in which the shapes and areas of facilities are changed dynamically. Two facility-swapping methods and two local search methods help hybrid algorithm escape from local optima, allowing a more reliable solution. Moreover, a new shifting method is developed to prevent the spatial overlapping between adjacent facilities and save material handling costs. The performance of the hybrid algorithm is confirmed by some test problems available. Finally, the proposed method is extended to a facility layout planning of a new aircraft assembly shop floor. Computational results show that the efficiency and effectiveness of the proposed method, in sharp comparison with other approaches.