The aim of this investigation was to evaluate the effect of etching protocols on bond strength, surface roughness, and mechanical properties of a zirconia-reinforced lithium silicate (ZLS) CAD/CAM-ceramic. In total, 100 bars (ISO 6872), 75 plaques, and 25 cubes were cut from ZLS blocks(Vita Suprinity®). The surfaces were standardized, crystallized and divided into five groups: 1. control (no/treatment-C), 2. 5%-Hydrofluoric-acid (HF)/20 s (HF5%20s), 3.HF5%60s, 4.HF10%20s, and 5.HF10%60s. Flexural strength (FS) (three-point bending test, 1 mm/min), roughness (Pa), and micro-shear bond-strength (µSBS) tests were performed. The data were statistically analyzed with one-way ANOVA, Tukey's test (p ˂ 0.05) and Weibull (FS data). C showed higher Pa (1.176 ± 0.370 µm) than HF10%60s (0.627 ± 0.236 µm) and all other groups. Groups C and 20 s showed the most irregular surface patterns. The FS results were not influenced by etching protocols, while the Weibull modulus was, with the 5%HF groups being the most reliable (m: 5.63/6.70), while C and HF10%60s (m: 2.78/2.73) were the least reliable. All fractures originated from surface defects on the treated side of specimens. The 5%HF groups showed higher µSBS (20 s: 21.35 ± 4.70 MPa; 60 s: 23.50 ± 4.27 MPa) than the 10%HF groups (20 s: 14.51 ± 2.47 MPa; 60 s: 16.54 ± 3.12 MPa) and C (6.46 ± 2.71 MPa). The most prevalent failure pattern was "mixed" for etched groups, and "adhesive" for C. Etching protocols affect the evaluated properties by roughening materials' surface and, in some cases, regularizing surface defects. The best overall outcomes were achieved when applying 5%HF.