Abstract：Albert Einstein ever said that the mere formulation of a problem is far more essential than its solution, which may be merely a matter of mathematical or experimental skills. To raise new questions, new possibilities, to regard old problems from a new angle require creative imagination and marks real advances in science. Thus, finding problems is likely to be more valuable than solving problems in our life. There have been many researches about the creative problem solving, especially including about studies of neural mechanisms. However, less attention has been paid on the issue of problem finding. Hence, it’s necessary to research the neural mechanism of problem finding. When facing similar problem situation but different heuristic prototypes, people may find different valuable levels of problem. Scientific problems can lead one to acquire new thoughts on problem solving; Normal problems can only help us to get to know the problem goals but no clue. But whatever problem it finds, it will include the basic process of problem finding. In addition, the heuristic prototypes which participants learned recently or storage in brain previously may have difference in scientific valuable problem finding. As for the neural mechanism, Brain-imaging techniques such as functional magnetic resonance imaging (fMRI) have made it possible for us to record precisely the brain activation associated with problem finding. Therefore, in the present study, using real life scientific innovations materials and fMRI techniques to explore the brain mechanisms of problem finding. In this study, 76 problem situations (on scientific innovation) were selected as materials. Of the 76 problem situations selected, 36 have related prototype and 40 do not have related prototype. The learning-testing paradigm was used to explore the brain mechanisms of problem finding with fMRI. Participants were asked to find a problem based on the given problem situation. Behavior date showed the mean accuracy rate was extremely significant higher for finding scientific problems with heuristic knowledge than without heuristic knowledge [t (17) = 8.12, p < 0.001]. And our fMRI data showed that the contrast between finding scientific problem with heuristic prototype and finding normal problem without heuristic prototype resulted in common activation in the left precentral gyrus (BA 44), the left medial frontal gyrus (BA 6), the left fusiform gyrus (BA 19), the left lentiform nucleus and the right cerebellum; The contrasts between finding scientific problems with related heuristic prototype and finding scientific problems without related heuristic prototype resulted in significant activation in the left precuneus (BA 7), the left inferior frontal gyrus (BA 10) and the left middle temporal gyrus (BA 39). Based on these results above, the common activation showed that: (1) the left fusiform gyrus might be responsive to the semantic processing of each sentence. (2) The left medial frontal gyrus might be associated with the entire semantic processing and “problem finding” existed in inter-semantic (the left lentiform nucleus and the right cerebellum might be separately involved in the directing of attention and allocating attention resources). (3) The left precentral gyrus might be responsible for expressing “the problem” existed in inter-semantic in language sentence; the significant activation showed that: (1) the left precuneus might be involved in the automatic retrieve of episodic memory. (2) The left inferior frontal gyrus might be associated with cognitive control. (3) The left middle temporal gyrus might be related to the automatic activation of novel heuristic prototype.