The minimum vertex cover problem (MVCP) is one of the well-known NP-complete problems that can be used to formulate numerous real-life applications. The MVCP has been solved using different approaches, exact, heuristic, and metaheuristic. Chemical reaction optimization (CRO) is a population-based metaheuristic algorithm that simulates what happens in chemical reactions to solve many problems. In this paper, the MVCP is solved using hybridization of a modified version of the CRO algorithm and the best-first search (BFS) algorithm. This hybridization is symbolized by MCROA-BFS. The BFS algorithm is exploited to generate initial populations with high-quality initial solutions in comparison with the random bit-vector (RBV) approach as a traditional approach for generating initial populations for several population-based metaheuristic algorithms. At first, the MCROA is evaluated analytically in terms of run time complexity. Then the performance of the MCROA is evaluated experimentally to sh