Proteins are biopolymers of highly varied structures taking part in almost all processes occurring in living cells. When nanoparticles (NPs) interact with proteins in biological environments, they are surrounded by a layer of biomolecules, mainly proteins adsorbing to the surfaces. This protein rich layer formed around NPs is called the “protein corona”. Consequential interactions between NPs and proteins are governed due to the characteristics of the corona. The features of NPs such as the size, surface chemistry, charge are the critical factors influencing the behavior of protein corona. Molecular properties and protein corona composition affect the cellular uptake of NPs. Understanding and analyzing protein corona formation in relation to protein-NP properties, and elucidating its biological implications play an important role in bio-related nano-research studies. Protein-NP interactions have been studied extensively for the purpose of investigating the potential use of NPs as carriers in drug delivery systems. Further study should focus on exploring the effects of various characteristic parameters, such as the particle size, modifier type, temperature, pH on protein-NP interactions, providing toxicity information of novel NPs. In this contribution, important aspects related to protein corona forming, influential factors, novel findings and future perspectives on protein-NP interactions are overviewed. •Protein-corona formation around nanoparticles•Literature review on nanoparticle-protein interactions•Up-to-date development on protein adsorption•Critical analysis of physico-chemical factors•Future perspectives