The invention provides an anti-interference circuit packaging structure, and belongs to the field of digital circuit design. The anti-interference circuit packaging structure comprises an upper substrate of which the top surface is provided with a top component and the bottom surface is provided with a bottom component; a lower substrate which is arranged at the bottom of the upper substrate witha hollow middle part; and a metal shielding cover which covers the top component and is fixedly connected with the top surface of the upper substrate. The anti-interference circuit packaging structurehas a very significant improvement effect on the spatial shielding isolation and anti-interference of the digital circuit and is small in volume so as to facilitate the miniaturization design and application of the circuit packaging structure. The invention also provides a manufacturing method of the anti-interference circuit packaging structure. The manufacturing method comprises the steps of manufacturing the upper substrate and the lower substrate and leaving the middle part of the lower substrate empty; fixedly connecting and conductively connecting the upper substrate and the lower substrate; installing the top component and the bottom component respectively; and covering the metal shielding cover on the top component to be fixedly connected on the top surface of the upper substrate.The manufacturing method has simple operation process and high process compatibility and is beneficial to the manufacturing cost of the circuit packaging structure.