This paper proposes a hybrid scheme to set the weights initialization and the optimal number of hidden nodes of the backpropagation network (BPN) by applying the loading weights and factor numbers of the partial least-squares (PLS) algorithm. The joint PLS and BPN method (PLSBPN) starts with a small residual error, modifies the latent weight matrices, and obtains a near-global minimum in the calibration phase. Performances of the BPN, PLS, and PLSBPN were compared for the near infrared spectroscopic analysis of glucose concentrations in aqueous matrices. The results showed that the PLSBPN had the smallest root mean square error. The PLSBPN approach significantly solves some conventional problems of the BPN method by providing the good initial weights, reducing the calibration time, obtaining an optimal solution, and easily determining the number of hidden nodes.