Custirsen is the second-generation antisense oligonucleotide (ASO), which can reduce cellular levels of clusterin to increase the cytotoxic effect of chemotherapeutic drugs. Our study assessed the efficacy and safety of custirsen in patients with metastatic castration-resistant prostate cancer (mCRPC).We conducted a comprehensive search to identify all the randomized controlled trials (RCTs) of custirsen for the treatment of mCRPC. The reference lists of the retrieved studies were investigated.Three publications involving a total of 1709 patients were used in the analysis. We found that overall survival (OS) (P = .25) was not statistically significant in the comparison. Safety assessments indicated custirsen were often associated with complications resulting from neutropenia (P < .001), anaemia (P < .001), thrombocytopenia (P < .001), and diarrhea (P = .002).Our meta-analysis shows that custirsen has no obvious effect on improving the OS of patients with mCRPC. Adverse reactions were more common among those patients treated with custirsen as compared to those treated with placebo.