Hepatocellular carcinoma (HCC) recurrence is one of the leading causes of death after orthotopic liver transplantation (OLT). The sixth complement component (C6) is a late-acting complement protein that participates in the assembly of the membrane attack complex, which has an indispensable role in innate and acquired immune responses, as well as cancer immune surveillance. However, studies assessing the association between C6 and HCC recurrence after OLT are scarce. This study aimed to evaluate the association of donor and recipient C6 single-nucleotide polymorphisms with the risk for HCC recurrence after OLT. A total of 71 adult patients who underwent primary LT for HCC were enrolled. HCC recurrence was observed in 26 (36.6%) patients. Ten single-nucleotide polymorphisms were genotyped and analyzed in both donor and recipient groups. Patients with the rs9200 heterozygous GA variant presented significantly higher HCC recurrence rates (54.17 vs 27.66%, P = 0.028), and lower cumulative tumor-free survival and overall survival (P = 0.006 and P = 0.013, respectively) compared with those harboring the GG/AA genotype, in multivariate logistic regression and Cox regression analyses. The rs9200 heterozygous GA variant in C6 persisted as a statistically independent prognostic factor (P < 0.05) for predicting HCC recurrence after OLT. In conclusion, recipient C6 rs9200 polymorphism is associated with HCC recurrence after OLT, and improves the predictive value of clinical models.