Abstract Single-cell CRISPR screens have been widely used to investigate gene regulatory circuits in diverse biological systems. The recent development of single-cell CRISPR screens has enabled multimodal profiling of perturbed cells with both gene expression, chromatin accessibility and protein levels. However, current methods cannot meet the analysis requirements of different types of data and have limited functions. Here, we introduce Single-cell CRISPR screens data analysEs and perturbation modEling (SCREE) as a comprehensive and flexible pipeline to facilitate the analyses of various types of single-cell CRISPR screens data. SCREE performs read alignment, sgRNA assignment, quality control, clustering and visualization, perturbation enrichment evaluation, perturbation efficiency modeling, gene regulatory score calculation and functional analyses of perturbations for single-cell CRISPR screens with both RNA, ATAC and multimodal readout. SCREE is available at https://github.com/wanglabtongji/SCREE.