The facility layout problem (FLP) is a very important class of NP-hard problems in operations research that deals with the optimal assignment of facilities to minimize transportation costs. The quadratic assignment problem (QAP) can model the FLP effectively. One of the FLPs is the hospital facility layout problem that aims to place comprehensive clinics, laboratories, and radiology units within predefined boundaries in a way that minimizes the cost of movement of patients and healthcare personnel. We are going to develop a hybrid method based on discrete differential evolution (DDE) algorithm for solving the QAP. In the existing DDE algorithms, certain issues such as premature convergence, stagnation, and exploitation mechanism have not been properly addressed. In this study, we first aim to discover the issues that make the current problem worse and to identify the best solution to the problem, and then we propose to develop a hybrid algorithm (HDDETS) by combining the DDE and tabu search (TS) algorithms to enhance the exploitation mechanism in the DDE algorithm. Then, the performance of the proposed HDDETS algorithm is evaluated by implementing on the benchmark instances from the QAPLIB website and by comparing with DDE and TS algorithms on the benchmark instances. It is found that the HDDETS algorithm has better performance than both the DDE and TS algorithms where the HDDETS has obtained 42 optimal and best-known solutions from 56 instances, while the DDE and TS algorithms have obtained 15 and 18 optimal and best-known solutions out of 56 instances, respectively. Finally, we propose to apply the proposed algorithm to find the optimal distributions of the advisory clinics inside the Azadi Hospital in Iraq that minimizes the total travel distance for patients when they move among these clinics. Our application shows that the proposed algorithm could find the best distribution of the hospital’s rooms, which are modeled as a QAP, with reduced total distance traveled by the patients.