Abstract For effective analysis of a small amount of liquid samples such as a single-droplet, surface-enhanced laser-induced breakdown spectroscopy (LIBS) can be considered. In this method, a drop of liquid sample is placed on the solid substrate, dried, and then analyzed by LIBS. However, the dry residues are distributed inhomogeneously and moreover concentrated in a very small area on the substrate surface. This uncontrollable distribution of analytes was identified as one of the main factors deteriorating the surface-enhanced LIBS analysis performances. We demonstrated the effectiveness of a newly devised laser-patterned silicon wafer (LPSW) with 40 × 40 crossed 1-cm laser-produced trenches in improving the analytical performances of surface-enhanced LIBS. The LPSW substrate spreads dry residues more homogeneously in the well-defined area (1 × 1 cm). This significantly reduces the heterogeneous saturation of the analyte and reference line intensities. In comparison with the results using bare silicon wafer substrates, linear dynamic range of the calibration curve, analysis precision, and sampling efficiency were greatly improved by the LPSW substrates. For the analysis of potassium ion dissolved in a 15-μL water droplet, the limit of detection of 0.23 × 10 − 9 mol and the analysis precision of ~ 4% relative standard deviation were obtained using the LPSW substrates. Consequently, the benefits from the LPSW substrates allow multiple repeatable measurements for a single aqueous solution droplet sample.