In vivo proteins can efficiently fold into their native states to perform their functions.However,the physical mechanism of this efficient folding is still not well understood.A lot of solutions have been proposed to solve this problem.The key point of all these proposals is how to reduce the dimensionality of conformational space that a protein needs to search.Levinthal suggested a nucleation mechanism1.Similar point of view was also proposed by Dill et al2.From the point of view of computational complexity3,4,the paradox could be solved if only near-neighbor in-teractions of each amino acid were involved.Here we show that cell has developed a special way to solve the problem of protein folding efficiency.The confined-space folding in the ribosomal exit tunnel and co-releasing folding from the tunnel restrict-ed the conformational space searching by proteins and guaranteed the formation of stable local interactions.This greatly reduced the dimensions of the conformational space searched by proteins and makes them fold along a well-defined pathway.Our results indicate that the folding environment and manners are important for efficient protein folding.We should focus not only on proteins themselves but also their fold-ing manners and environments in order to solve the protein folding problem.