This study was designed to evaluate and compare the stability, antioxidant and anticancer activities of selenium nanoparticles (SeNPs) decorated with different molecular weight (MW) of chitosan (CS) (1500Da, 48 kDa, 510 kDa). The size range of well-dispersed SeNPs was effectively controlled by I first and then coated with CS. The morphology, size and surface charge of generated SeNPs were characterised by several technologies. Fourier transform infrared spectroscopy was used to investigate the relationship between SeNPs and CS. SeNPs decorated with CS (510 kDa) can keep stable for more than 45 days. As observed from the results of a simple photometric system, the antioxidant activities of decorated SeNPs were enhanced compared to undecorated SeNPs. SeNPs coated with higher MW of CS (510 kDa) showed the strongest antioxidant activities. Moreover, the treatments of SeNPs decorated with CS inhibited the growth of HepG2 cells in a time- and dose-dependent manner. The proposed results demonstrated the critical roles of the MW of CS on the stability, antioxidant and anticancer properties of CS-coated SeNPs, which provided an important design cue for future applications of functional foods and additives.