In this paper, a dynamical model of malaria transmission with vector-bias and timedependent controls is investigated. The controls include the RTS,S malaria vaccine, using insecticide-treated mosquito net, treatment of infectious human, and indoor spraying. For constant controls, the existence and stability of equilibrium, as well as the existence of backward bifurcation, are obtained. The sensitivity analysis quantifies the impact of parameters and controls on the basic reproduction number. For time-dependent controls, by using the Pontryagin’s maximum principle the existence and expression of optimal controls are established. As an application of the model and control strategies, the malaria transmission and controls in Democratic Republic of Congo are discussed. To be specific, we simulate the reported cases of Democratic Republic of Congo by World Health Organization and predict the trends. Cost-effectiveness analysis and numerical simulations show that combining all controls can minimize the number of infected humans to the full extent, using insecticide-treated mosquito net is the most cost-effectiveness strategy, combining RTS,S malaria vaccine with using insecticide-treated mosquito net and treatment of infectious human is also cost-effective among all the strategies with good effect.