Significance Plant cytoplasmic male sterility (CMS) and sterility restoration by nuclear restorer-of-fertility ( Rf ) genes provide a crucial breeding tool to harness hybrid vigor in many crops. Here, we identify RF6 as a novel pentatricopeptide repeat family protein that restores the fertility of Honglian CMS (HL-CMS), a major type of rice CMS used in breeding. We demonstrated that RF6 and hexokinase 6 function together in mitochondria to promote the processing of the aberrant CMS-associated transcript atp6-orfH79 , thereby restoring the fertility of HL-CMS rice. This study links CMS restoration to hexokinase, providing novel insights into the mechanisms of CMS restoration, pollen development, mitochondria metabolism, and nuclear-cytoplasmic communication. In addition, the present study offers opportunities to further exploit rice heterosis in hybrid rice production.