Molecular Biology makes it possible to express foreign genes in microorganism, plants and animals. To improve the heterologous expression, it is important that the codon usage of sequence be optimized to make it adaptive to host organism. In this paper, a novel method based on Quantum-behaved Particle Swarm Optimization (QPSO) algorithm is developed to optimize the codon usage of synthetic gene. Compared to the existing probability methods, QPSO is able to generate better results when DNA/RNA sequence length is less than 6Kb which is the commonly used range. While the software or web service based on probability method may not exclude all defined restriction sites when there are many undesired sites in the sequence, our proposed method can remove the undesired site efficiently during the optimization process.