In the present study, we demonstrated the novel role of UCA1 in GBC and figured out that: a) UCA1 was upregulated in GBC; b) the upregulation of UCA1 was related to the tumor size, lymph node metastasis, TNM stage and overall survival of GBC patients; c) UCA1 promoted GBC cell proliferation and metastasis; d) UCA1 promoted tumorigenicity in nude mice; e) UCA1 played a pivotal role in GBC cell proliferation and metastasis through epigenetically regulating the expression of p21 and E-cadherin by interacting with EZH2. Here, CDKN1A is linked to neoplasm.