Microfibrillated cellulose (MFC) was obtained by mechanical grinding of different pulps. MFC-modified ground calcium carbonate (GCC) was prepared in two different ways, designated MFC-GCC composite filler and MFC-GCC flocs filler. The opacity of pulp handsheets loaded with MFC-modified GCC was measured. The effects of MFC originated from different pulps, pretreatment method, and filler modification on the opacity of handsheets loaded with MFC-modified GCC were discussed. The results show that MFC originated from alkaline peroxide mechanical pulp (APMP) was optimal for improving the opacity of the handsheets and PFI grinding pretreatment for MFC provided a denser structure in the corresponding MFC_APMP-GCC floc filler while enzyme pretreatment was more effective in increasing the opacity of the filled paper. Under the experimental conditions, the opacity of handsheets increased from 81.0% to 82.7% when the unmodified GCC was replaced by an equivalent amount of MFC_APMP-GCC composite filler, while other properties were unchanged.