Bioluminescence tomography (BLT) has become a hot topic over in recent years. In this paper, a hybrid genetic reconstruction algorithm (HGA) based on quadratic penalty function is presented for BLT inverse problem. Simulation results of the single and multiple sources are reported in a molecular optical simulation environment (MOSE) which we developed to simulate the photon transportation of optical imaging in living organisms. Comparing with genetic algorithm (GA), the illustrations indicate that HGA is feasible and effective for BLT source reconstruction.