The purpose of this in vitro study was to compare the shear bond strengths (SBSs) of two newly marketed self-adhesive resin cements (RCs) to enamel, dentin, and lithium disilicate (LiSi) glass ceramic block. Forty-eight enamel and 48 dentin substrates were obtained from sound human molars. Additionally, 6 x 7 x 5 -mm- sized 24 specimens were produced from LiSi glass ceramic blocks. The tooth specimens were randomly assigned into four groups (n = 12) according to the surface treatments: (1) G-CEM ONE (GCO), (2) G-CEM ONE Adhesive Enhancing Primer (GCO-AEP) + GCO, (3) RelyX Universal (RXU), and (4) Scotchbond Universal Plus (SUP) + RXU. LiSi specimens were randomly divided into two groups (n = 12): (1) G-MultiPrimer (GMP) + GCO and (2) SUP + RXU. Following the RC applications, all specimens were kept in 100% humidity at 37 degrees C for 24 hr and then submitted for SBS testing in a universal testing machine (1 mm/min). Data were analyzed by Welch's, one-way analysis of variance and two independent samples t tests. The nature of failures was examined under a light microscope, and scanning electron microscopy analyses were also performed for interfaces. GCO and RXU showed similar SBS to enamel (p > .05), and the use of adhesives resulted in improved SBS (p < .05). No difference was detected between GCO-AEP + GCO and SUP + RXU. The GCO-AEP + GCO exhibited the highest SBS to dentin (p < .05), followed by GCO >= SUP + RXU > RXU (p < .05). There was no significant difference between SBSs of two RCs to LiSi blocks (p > .05). No cohesive failure was determined for the tested groups by light microscope. The use of adhesives prior to the application of self-adhesive RCs improved their bonding to tooth tissues. GCO demonstrated superior SBS to dentin, whereas both self-adhesive RCs generated similar SBS to enamel and LiSi glass ceramic surfaces.