Abstract Background Prodynorphin (PDYN) gene polymorphisms have been linked with opioid dependence (OD) with conflicting outcomes, the aim of this study is to synthesize the existing evidence of the association between PDYN polymorphisms and OD susceptibility. Methods Four databases including PubMed, EMBASE, Web of Science, and Wanfang were retrieved for relevant studies before August, 2018. All identified studies were evaluated using predetermined inclusion and exclusion criteria. Summary odds ratio (OR) and 95% confidence interval (95%CI) were calculated to appraise the association. Statistical analysis was performed using RevMan 5.3 software. Results A total of seven case-control studies with 3129 cases and 3289 controls were recruited in the meta-analysis. For rs910080, rs1997794, rs1022563, and rs2235749 polymorphisms of PDYN gene, there were six, four, five, and four studies eventually included, respectively. The findings indicated that rs910080 polymorphism was significantly correlated with OD among Asian population under allelic model (A vs. G, OR = 1.30, 95% CI 1.04–1.62, P = 0.02, FDR = 0.05) and dominant model (AA+AG vs. GG, OR = 1.25, 95% CI 1.04–1.51, P = 0.02, FDR = 0.05). However, rs1022563, rs1997794 and rs2235749 polymorphisms did not appear to associate with OD susceptibility. Conclusions There existed a significant association between rs1022563 polymorphism and OD among Asian population. As the included studies were not adequate to guarantee a robust and convincing conclusion, future studies with larger sample size among more ethnicities are recommended.