Synthetic lethality describes an interaction whereby the co-occurrence of two mutations leads to cell death but one mutation alone does not, which can be exploited for cancertherapeutics. Due to lacking effective nonsurgical treatment and early clinical diagnosis markers, patients have high mortality and low overall survival rates in cholangiocarcinoma (CCA). Based on our previous predicted results in CCA (SLOAD, http: //tmliang.cn/SL), ARID1A: ALDH2 is a pair gene with synthetic lethal. Thus, the involvement of ARID1A in maintaining genome stability makes it a potential candidate for synthetic lethal therapy of ARID1A-deficient tumors. ALDH2 belongs to aldehyde dehydrogenase (ALDH) family. Endogenous aldehyde accumulation is considered as an important source of cellular reactive oxygen species (ROS). The synthetic lethal interaction between ARID1A and ALDH2 was detected in 11 cancer types. Simultaneously, the synthetic lethal interaction was also screened in another research. Finally, the common ARID1A: ALDH2 gene pair in the two datasets was selected for further experimental validation. We cultured CCA cells (HCCC9810 and HuCCT1) in vitro and constructed the stable cell lines of ARID1A knockout and cooperate with ALDH2 inhibitor (disulfiram, DSF) to explore whether there was synthetic lethality between ARID1A and ALDH2. Cell cloning experiment showed that there were no significant changes on growth rate of CCA cells after ARID1A knockout or treatment with DSF. However, after treatment with DSF, there was markedly inhibition on the survival of CCA cells in the case of ARID1A knockout (P < 0.05).