This article evaluates the etching efficacy of a self-etching ceramic primer (SECP) on zirconia-reinforced lithium silicate (ZLS) ceramics. Celtra Duo (DeguDent GmbH, Hanau-Wolfgang, Germany) and Vita Suprinity (Vita Zahnfabrik, Bad Säckingen, Germany) were used in this study. A total of 36 ceramic slices were prepared from each ceramic material and randomly distributed into three groups according to the surface treatment applied (n = 12 per group). Group 1 (polished) was polished with silicon carbide paper discs and did not undergo any surface treatment; group 2 (SECP) was surface treated with SECP (Monobond Etch and Prime, Ivoclar Vivadent, Schaan, Liechtenstein); group 3 (hydrofluoric acid [HF]) was surface treated with 4.7% HF etching. Half of the specimens (n = 6) from each group were gold-sputtered, and the surface topographic alterations were evaluated by scanning electron microscopy at magnifications of 5,000× and 10,000 × . The surface roughness of the other half (n = 6) from each group was tested using a three-dimensional optical profiler. Data were statistically analyzed using two-way analysis of variance and Tukey's multiple comparisons test. Both SECP and HF etching surface treatments resulted in a statistically significant increase (p < 0.05) in the surface roughness of both ceramic materials, compared to that of their respective control group specimens (polished). HF etching resulted in a significant dissolution of the glassy phase of each ceramic. SECP can effectively etch ZLS ceramics. The etching patterns created after the application of SECP were mild compared to those produced by HF etching. The topographic surface features of ceramics are affected by both, surface treatment and material composition.