Abstract: 3D packaging has become the important way for the further integrate of electronic systems. In order to meet the miniaturization requirements of radio frequency system, a 3D System-in-Packaging (SiP) of RF system is designed and implemented by using flexible substrate as three-dimensional vertical interconnection. The size of the package is 50mm*52.5mm*8mm, almost reducing the area 20 times compare to the prototype. HFSS and SIwave are used to design and optimize the signal integrity(SI) and power integrity(PI) of the system. The simulation results show that the insertion loss of the critical clock is less than 0.31dB, the return loss is more than 15 dB, and the eye quality is good. Meanwhile, the Power distribution network(PDN) impedance meets the design requirements.