Runt related transcription factors as trans-acting elements play critical roles in the developmental control of cell fate, hematopoiesis, bone formation and cancers. In previous study, the homologue of runt related transcription factor PmRunt has been identified from pearl oyster Pinctada fucata martensii and considered to play an important role in nacre formation. In this study, we used the same samples to perform RNA-seq to detect the global effects after the decrease of PmRunt expression. The transcription levels of several nacre shell matrix protein (NSMP) genes were significantly changed and the potential compensatory effect could happen internal gene families. Downregulation of PmRunt could also influence the biosynthesis of NSMPs through affecting amino acid metabolism, translation, protein processing and export. The inhibition of PmRunt also possibly affected the expression of caspases, IAPs and C1qs that related to apoptosis and immune. In addition, PmRunt highly expressed at 12 h and 12 d after transplantation in hemolymph, which was corresponded to transplantation immunity immune response and the morphology of pearl sac, suggested the cross-talk of biomineralization-immune regulation in hemocytes. Furthermore, a lincRNA (LncRunt) that co-located with PmRunt was identified and showed a significantly relative expression with PmRunt, which suggested the potential regulation. Therefore, these findings provided new idea to find the regulation targets of runt-related transcription factors and offers evidence of lncRNAs in potential biomineralization-immune regulation.