AbstractThe powdered cement tetracalcium phosphate/monetite/silk fibroin composite (CFIB) was prepared by simple mechanical milling of tetracalcium phosphate/monetite powder mixture with fibrous soluble silk fibroin (SF). The powder composite cement mixtures contained 5 and 10 wt % of SF and 2% NaH₂PO₄ solution with 0.1% genipin was used as a liquid component. The setting time of CFIB cement increased with addition of SF from 5 to 25 min in fully injectable cement with 10 wt % of SF. The compressive strength of hardened composites was reduced to 14 MPa which is close to strength of cancellous bone. The 8% of SF from origin amount in CFIB composites was only desorbed from cements after 7 days soaking in simulated body fluid (SBF). It was found almost full transformation of calcium phosphate components in composite to rod‐like nanohydroxyapatite after hardening of CFIB cements in SBF. The SF in hardened cements was present in fine globular form after dissolution, actively affected the fluidity of pastes, morphology of hydroxyapatite particles, and microstructure. The excellent cell proliferation and a high over expression of osteogenic gene markers in MSCs were confirmed after the long‐time cultivation in CFIB10 cement extract. Injectable CFIB10 cements have appropriate properties for utilization in bone defect treatments with possible positive effect on healing process.