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The plant protein phosphatase 2Cs (PP2Cs) play an essential role in response to stress and abscisic acid (ABA) signaling pathway. However, to date, no systemic characterization of the PP2Cs has yet been conducted in potato (Solanum tuberosum L.). In the study, a comprehensive research was performed on genome-wide identification and expression analysis of StPP2C genes in potato. A total of 78 potato StPP2C genes were identified based on specific structure of PP2C domain, which were distributed across 11 out of 12 potato chromosomes and divided into 12 (A-L) phylogenetic branches. The result from gene duplication analysis showed that 14 StPP2Cs were involved in gene tandem duplication and 8 genes formed fragment duplication events, which indicated that both tandem and fragment duplication contributed to the expansion of the gene family in evolution. Exon-intron structural analysis showed that they had a wide range of exon numbers. Analysis of protein conservative motif demonstrated that StPP2Cs contained more similar motif structures in the same phylogenetic branches. The cis-elements in StPP2C gene promoter regions were mainly responded to light, phytohormone and abiotic stress. Most of them exhibited tissue-specific expression patts, and some members could differentially express under abiotic stress. The evidence suggested that StPP2C genes may contribute to different functions in several physiological stress and environmental stress conditions. This study could provide new insights to further investigate StPP2C functional characteristics responding to various stresses in potato.