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Abstract BMS‐986263 is a retinoid‐conjugated lipid nanoparticle delivering small interfering RNA designed to inhibit synthesis of HSP47 protein, a collagen‐specific chaperone protein involved in fibrosis development. This is a phase I, open‐label, two‐part study evaluating pharmacokinetics and safety of BMS‐986263 in participants with hepatic impairment (HI). Part 1 (n = 24) of this study enrolled two cohorts with mild and moderate HI and a separate cohort of age‐ and body mass index (BMI)‐matched participants with normal hepatic function. Part 2 enrolled eight participants with severe HI and eight age‐ and BMI‐matched participants with normal hepatic function. All participants received a single intravenous 90 mg BMS‐986263 infusion. Compared with normal‐matched participants, geometric mean area under the plasma concentration‐time curve time zero to the time of the last quantifiable concentration (AUC(0‐T)) and AUC from zero to infinity (AUC(INF)) of HSP47 siRNA were similar in participants with mild HI and 34% and 163% greater in those with moderate and severe HI, respectively, whereas the maximum plasma concentration was ~25% lower in mild and moderate HI groups but 58% higher in the severe HI group than in the normal group. Adverse events were reported by two of eight, four of eight, and three of eight participants with mild, moderate, or severe HI, respectively; none were reported in the normal‐matched group. Overall, single‐dose BMS‐986263 was generally safe and well‐tolerated and dose adjustment is not considered necessary for participants with mild or moderate HI. Although available data do not indicate that dose adjustment should be performed in patients with severe HI; the optimal posology of BMS‐986263 in patients with severe HI may be determined later in its clinical development when additional data to establish exposure‐safety/efficacy relationship becomes available.