Disclosed are an 8-arm polyethylene glycol (PEG) derivative (formula 1), manufacturing method and modified bio-related substance thereby, wherein a tetravalent group U and four trivalent groups E c form a highly symmetric octavalent central structure CORE 0 together, L c connects the octavalent center to eight PEG arms having polydiversity or monodiversity and having n 1 -n 8 as the degrees of polymerization thereof. The terminal of one PEG chain is connected to at least one functional group F (k ‰¥ 1), and said PEG chain and F can be directly connected (g = 0) or connected with a divalent linking group L 0 connected with a terminal branched group G (g = 1) therebetween. The latter provides more reacting sites to combine more pharmaceutical molecules, thereby increasing the drug loading capacity. The near-center symmetric structure of the derivative allows more precise control over the molecular weight during large-scale production, thereby facilitating acquisition of a product having a narrower molecular weight distribution. A bio-related substance modified thereby has a more uniform and controllable performance.