This paper presents a hybrid wearable bio-sensing system, which combines traditional small-area low-power and high-performance System-on-Chip (SoC), flexible paper substrate and cost-effective Printed Electronics. Differential bio-signals are measured, digitized, stored and transmitted by the SoC. The total area of the chip is 1.5 × 3.0 mm(2). This enables the miniaturization of the wearable system. The electrodes and interconnects are inkjet printed on paper substrate and the performance is verified in in-vivo tests. The quality of electrocardiogram signal sensed by printed electrodes is comparable with commercial electrodes, with noise level slightly increased. The paper-based inkjet printed system is flexible, light and thin, which makes the final system comfortable for end-users. The hybrid bio-sensing system offers a potential solution to the next generation wearable healthcare technology.