Purpose: To evaluate the effect of different concentrations of hydrofluoric acid (HF) on the surface roughness of a ceramic reinforced by lithium disilicate and on the bond strength formed between the ceramic and self-adhesive resin cement. Materials and Methods: A total of 100 disks of IPS e.max Press ceramic (Ivoclar Vivadent) reinforced by lithium disilicate were prepared as follows: group 1 remained untreated (control group); in groups 5-20, 5-40, and 5-60, the surfaces were etched with 5% HF for 20, 40, and 60 seconds, respectively; in groups 10-20, 10-40, and 10-60, the surfaces were etched with 10% HF for 20, 40, and 60 seconds, respectively; and in groups 10-20P, 10-40P, and 10-60P, the surfaces were etched with 10% HF for 20, 40, and 60 seconds, respectively, followed by treatment with 37% phosphoric acid for 5 seconds. Surface roughness and bond strength were analyzed with confocal microscopy and microshear testing, respectively. The values obtained were statistically analyzed using paired t test and two-way ANOVA followed by Tukey post hoc test at a 5% significance level. Results: Surface roughness was influenced by the concentration and exposure time of acid applied (P .05) and by the combination of these two factors (P .05). Treatment with 10% HF for 40 seconds (group 10-40) achieved the highest roughness value. In contrast, bond strength was affected only by the acid exposure time (P .05). Conclusion: Conditioning of lithium disilicate ceramics can change the surface morphology, thereby affecting bond strength with resin cement.