Objective: To evaluate the release of Necrostatin-1 (Nec-1) in bone cement mixed by different proportions of calcium phosphate cement (CPC) and polymethyl methacrylate (PMMA) in vitro, and to optimize the mixture proportion of CPC-PMMA. Methods: CPC and PMMA powder are mixed at the ratio of 0:1, 1:1, 2:1, and 3:1, with 5.18 mg of Nec-1 as 4 groups (0:1 group, 1:1 group, 2:1 group, 3:1 group). The mixed bone cement samples are produced by same standard (height of 12 mm and an inner diameter of 6 mm). All the bone cement samples are tested by X-ray diffraction, compression test, solidification time, electron microscope scanning and the detection of Nec-1 release in vitro. The activity of releasing Nec-1 was deteted by culturing with MC3T3-E1 cells and then necrotic apoptosis cells were tested via Flow cytometry. Results: Nec-1, CPC and PMMA do not affect each other's material generation after the analysis of their mixture structure. With the increase of the proportion of CPC, the compressive strength of CPC-PMMA bone cement mixed with Nec-1 is gradually reduced and the time of solidification is prolonged. The distance between the PMMA particles in 0:1 group, 1:1 group, 2:1 group, and 3:1 group are about 0 mu m, 100200 mu m, 100-400 mu m, 100-400 mu m, respectively. By comparing the cumulative release of Nec-1 in the four groups, the release of 0:1 group is at the lowest level, and the rank of release rate is 3:1 group > 2:1 group > 1:1 group. It is clear that the release of Nec-1 is fast in 5 days in each group, become slower from 5 to 19 days and continuously decelerate after 19 days. The amount of Nec-1 release reaches the highest point at 19 days. The cumulative release concentration of Nec-1 of 0:1 group, 1:1 group, 2:1 group and 3:1 group in 59 days are 13.72 um/L, 286.66 um/L, 405.96 um/L and 553.77 um/L, respectively. The cumulative release percentages are respectively 0.34%, 7.17%, 10.15% and 13.84%. Through testing the necrotic apoptosis cells via Flow cytometry, the releasing Nec-1 still remains activity. Conclusions: This study has verified that CPC-PMMA bone cement mixture has a better comprehensive performance than simple PMMA bone cement, and established a methodology for detection of Nec-1 release in bone cement in vitro. In this study, Nec-1-CPC-PMMA bone cement mixture with the CPC to PMMA ratio of 3:1 showed the optimal compressive strength and coagulation time. And the mixture can release Nec-1 stably and the releasing Nec-1 maintains activity, thus this configuration would be an ideal choice for the preparation of a new type of Nec-1-CPC-PMMA bone cement.