Background The sequencing and annotations of cotton genomes provide strong theoretical support to reveal more physiological phenomena and functions. Plant homeodomain (PHD) protein family have been reported to be involved in regulating diverse biological processes in plants. However, their functions have not yet been carried out in cotton. Results In this study, we performed a genome-wide analysis of the PHD genes in cotton, including the chromosomal location, phylogenetic relationship, gene structure, and conserved domains. Using a phylogenetic analysis, we divided the 297 PHD genes into five subgroups. The GhPHDs were unevenly distributed across all 26 chromosomes in upland cotton, and whole genome duplication events analyses showed that purifying selection might contributed greatly to the maintenance of function in the GhPHD family. Expression pattern analysis based on RNA-seq data and qRT-PCR results showed that the most of GhPHD genes have significant tissue-specific spatial and temporal expression patterns, indicating GhPHD have multiple functions in growth and development. We further summarized the cis -acting elements in response to abiotic stresses and plant hormones, and treated cotton seedlings with abiotic stresses and plant hormones, respectively. Then, GhPHD gene expression level were detected by qRT-PCR, which indicated that GhPHD could response to stresses and plant hormones. Co-expression network analysis also indicated that GhPHDs were essential for plant growth and development, and phytohormone mediate GhPHD response to abiotic stress can improve plant tolerance to adverse environment. Conclusion This study provides useful information to facilitate the further study of the function of the GhPHD family.