The combined and interactive effects of the bolt-hole fit conditions and the preloads of the fasteners on the load carrying capacity of single-lap composite-to-titanium bolted joints have been investigated both experimentally and numerically. Quasi-static tests of the hybrid joints with different fit conditions are implemented, and a three dimensional finite element progressive failure analysis model is proposed to predict the influences of the bolt-hole fit conditions and fastener’s preloads on the mechanical behaviors of the joints. Based on the experimental validated simulation method, a multi-factor, mixed levels orthogonal design table and the analysis of variance method are used to arrange the simulation conditions and to further study the interactive effects of preloads and fit conditions. Through the analysis of the results, for the researched double bolt, single-lap composite-titanium joints, it is found that: the effects of both the interference fit and the preloads change from positive into negative mode with the increase of the interference fit values or preload values; appropriate bolt-hole fit conditions and preloads can improve the bolt-hole contact conditions of the loaded joints, and then retard the fiber failures around the fastener holes, and increase the load carrying capacity of the joints eventually; the interactive effect of the bolt-hole interference fit conditions and preloads cannot be ignored and the parameters need to be considered together and synthetically as the joints are being optimized. The combined and interactive effects of the bolt-hole fit conditions and the preloads of the fasteners on the load carrying capacity of single-lap composite-to-titanium bolted joints have been investigated both of the experimentally and numerically. Quasi-static tests of the hybrid joints with different fit conditions are implemented, and a three dimensional finite element progressive failure analysis model is proposed to predict the influences of the bolt-hole fit conditions and fastener’s preloads on the mechanical behaviors of the joints. Based on the experimental validated simulation method, a multi-factor, mixed levels orthogonal design table and the analysis of variance method are used to arrange the simulation conditions and to further study the interactive effects of preloads and fit conditions. Through the analysis of the results, for the researched double bolt, single- lap composite-titanium joints, it is found that: the effects of both the interference fit and the preloads change fr om positive into negative mode with the increase of the interference fit values ​​or preload values; appropriate bolt-hole fit conditions and preloads can improve the bolt-hole contact conditions of the loaded joints, and then retard the fiber failures around the fastener holes, and the load carrying capacity of the joints eventually; the interactive effect of the bolt-hole interference fit conditions and preloads can not be ignored and the parameters need to be considered together and synthetically as the joints are being optimized.