Objective To analyze the expression of HDAC1 in planarian, and explore the function and mechanism of HDAC1 in maintaining tissue homeostasis and planarian regeneration. Methods The full-length sequence of HDAC1 was acquired by rapid amplification of cDNA ends. The expression pattern of HDAC1 was determined by whole-mount in situ hybridization and Western blotting. The phenotype of planarian in tissue homeostasis and regeneration was determined after depleting HDAC1 by RNA interference. The expression of adult stem cell marker was assessed by immunofluorescence. Results The full-length sequence of HDAC1 was successfully cloned. Whole-mount in situ hybridization and Western blotting revealed that both HDAC1 transcripts and protein were highly enriched in planarian adult stem cells. Upon HDAC1 knockdown, planarian failed to maintain tissue homeostasis and regenerate missing body parts. Immunofluorescence with a stem cell marker showed that the number of adult stem cell also decreased significantly after HDAC1 knockdown. Conclusion HDAC1 gene plays important roles in maintaining planarian adult stem cells and promoting tissue regeneration.