The aim of this study was to evaluate the influence of different concentrations of hydrofluoric acid (HF) associated with varied etching times on the microshear bond strength (μSBS) of a resin cement to a lithium disilicate glass ceramic. Two hundred seventy-five ceramic blocks (IPS e.max Press [EMX], Ivoclar Vivadent), measuring 8 mm × 3 mm thickness, were randomly distributed into five groups according to the HF concentrations (n=50): 1%, 2.5%, 5%, 7.5%, and 10%. Further random distribution into subgroups was performed according to the following etching times (n=10): 20, 40, 60, 120, and 20 + 20 seconds. After etching, all blocks were treated with a silane coupling agent followed by a thin layer of an unfilled resin. Three resin cement cylinders (∅=1 mm) were made on each EMX surface, which was then stored in deionized water at 37°C for 24 hours before testing. The μSBS was in a universal testing machine at a crosshead speed of 1 mm/min until failure. Data were submitted to two-way analysis of variance, and multiple comparisons were performed using the Tukey post hoc test (α=0.05). One representative EMX sample was etched according to the description of each subgroup and evaluated using scanning electron microscopy for surface characterization. The HF concentrations of 5%, 7.5%, and 10% provided significantly higher μSBS values than 1% and 2.5% (p<0.05), regardless of the etching times. For 1% and 2.5% HF, the etching times from 40 to 120 seconds increased the μSBS values compared with 20 seconds (p<0.05), but etching periods did not differ within the 5%, 7.5%, and 10% HF groups (p>0.05). The effect of re-etching was more evident for 1% and 2.5% HF (p<0.05). Different HF concentrations/etching times directly influenced the bond strength and surface morphology of EMX.