The objective of this study was to explore the role of rs4705342 located in the miR‐143 promoter in relation to the control of HBV positive HCC and the underlying molecular mechanism. A luciferase assay was performed to explore the factors which influenced miR‐143 transcription activity and the target gene of miR‐143. This would further be confirmed by ChIP assay. Western blot and real‐time PCR were performed to identify the relationship between miR‐143 and ORP8. Luciferase activity of miR‐143 SNP was increased with the presence of C allele. The presence of T allele partially restored the transcription ability. NF‐κB displayed a much higher degree of luciferase activity in relation to the cells transfected with vectors containing either T or C allele rather than control cells with a greater extent in C allele group than T allele group. At the same time, ChIP assay indicated that the affinity of NF‐ΚB in the miR‐143 promoter was higher in C/C cells. The over‐expression of HBX promotes NF‐kB expression thus increasing the extent of binding of NF‐kB on the CC allele of the miR‐143 promoter. The binding is also abolished by NF‐kB siRNA. ORP8 was proven to be a target gene of miR‐143 using bioinformatics algorithm analysis. It was further confirmed by the luciferase assay that miR‐143 substantially inhibited luciferase activities of wild‐type ORP8. However, it did not affect the mutant ORP8. HBx induced by HBV infection up‐regulated miR‐143 expression. NF‐ kB can partially abolish the promotion effect of HBx on the miR‐143 level in cells genotyped as CC but not in cells genotyped as TT. Tissues derived from participants genotyped as CC exhibited a higher level of miR‐143, but a lower level of ORP8. The presence of the minor allele of rs4705342 in the promoter of miR‐143 attenuated the transcription ability. This promoted ORP8 expression and could be a factor contributing to the oncogenesis in HBV positive HCC.