Pseudo-range differential positioning is widely used in satellite navigation and position because of the cheap terminal, simple algorithm, no initialization of ambiguity and preferable precision. As the development of BDS/Galileo navigation system, the multi-GNSS combination will result in increasing the accuracy, reliability and availability of position. However, the multi-GNSS is almost loosing combining now, aware of the inter-system bias helps to reduce unknown parameters of positioning model and improve the performance of multi-GNSS positioning and the interoperability of different systems. This paper aimed at inter-system bias in GPS/GLONASS/BDS/Galileo navigation system in differential GNSS position. We analyzed the characteristic of double differenced ISB and the effect of differential GNSS when ISB is introduced. The results show that the day to day variation of double differenced ISB is less than 2 cm and the size of ISB is related to frequency of code and receiver type. When ISB is introduced, the precision and availability is obviously improved for the navigation and position in the complex circumstance liked urban canyon.