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Aims: Abiraterone acetate, a prodrug of abiraterone (ABI), provides an efficient therapeutic option for metastatic castration‐resistant prostate cancer patients. ABI undergoes extensive metabolism in vivo and is transformed into active metabolites Δ4‐abiraterone and 3‐keto‐5α‐abiraterone as well as inactive metabolites abiraterone sulfate and abiraterone N‐oxide sulfate. We aimed to examine the effect of polymorphisms in SLCO2B1, CYP3A4 and UGT1A4 on the pharmacokinetics of ABI and its metabolites. Methods: In this study, 81 healthy Chinese subjects were enrolled and divided into 2 groups for fasted (n = 45) and fed (n = 36) studies. Plasma samples were collected after administering a 250 mg abiraterone acetate tablet followed by liquid chromatography–tandem mass spectrometry analysis. Genotyping was performed on a MassARRAY system. The association between SLCO2B1, CYP3A4, UGT1A4 genotype and pharmacokinetic parameters of ABI and its metabolites was assessed. Results: Food effect study demonstrated high fat meal remarkedly increased systemic exposure of ABI and its metabolites. The geometric mean ratio and 90% confidence interval of area under the plasma concentration–time curve from time 0 to the time of the last quantifiable concentration (AUC0‐t) and maximum plasma concentration (Cmax) of ABI in fed state vs. fasted state were 351.64% (286.86%–431.04%) and 478.45% (390.01%–586.94%), respectively, while the corresponding results were ranging from 145.11% to 269.42% and 150.10% to 478.45% for AUC0‐t and Cmax of ABI metabolites in fed state vs. fasted state, respectively. The SLCO2B1 rs1077858 had a significant influence on AUC0‐t and Cmax, while 7 other SLCO2B1 variants prolonged half‐life of ABI under both fasted and fed conditions. As for ABI metabolites, the systemic exposure of Δ4‐abiraterone, abiraterone sulfate and abiraterone N‐oxide sulfate as well as the elimination of 3‐keto‐5α‐abiraterone were significantly affected by SLCO2B1 polymorphisms. Polymorphisms in CYP3A4 and UGT1A4 did not significantly affect pharmacokinetics of ABI and its metabolites. Conclusion: Polymorphisms in SLCO2B1 were significantly related to the pharmacokinetic variability of ABI and its metabolites under both fasted and fed conditions. [ABSTRACT FROM AUTHOR]