SUMMARY: Single-cell sequencing is an increasingly used technology and has promising applications in basic research and clinical translations. However, genotyping methods developed for bulk sequencing data have not been well adapted for single-cell data, in terms of both computational parallelization and simplified user interface. Here, we introduce a software, cellsnp-lite, implemented in C/C++ and based on well-supported package htslib, for genotyping in single-cell sequencing data for both droplet and well-based platforms. On various experimental datasets, it shows substantial improvement in computational speed and memory efficiency with retaining highly concordant results compared to existing methods. Cellsnp-lite, therefore, lightens the genetic analysis for increasingly large single-cell data. AVAILABILITY AND IMPLEMENTATION: The source code is freely available at https://github.com/single-cell-genetics/cellsnp-lite. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.