Abstract: The unique and in-depth professional technology accumulated by enterprises in specific knowledge fields for a long time is the key driving force to promote the breakthrough of key core technologies. This study takes the new generation of information technology industry in the first five batches of listed small giant enterprises in China as the research object, and deeply explores the effect and internal mechanism of technological specialization on the breakthrough of key core technologies. The results show that there is an inverted U-shaped relationship between technology specialization, knowledge search and key core technology breakthroughs. The inverted "U" shaped relationship between technology specialization and key core technology breakthroughs is mediated by knowledge search. Knowledge integration ability moderates the role of technology specialization and knowledge search on key core technology breakthroughs, respectively. High knowledge integration ability will alleviate the negative impact of over-specialization and over-search, and when it breaks through a certain threshold, it can completely offset the negative impact and further promote key core technology breakthroughs. This study emphasizes the complementary synergy between knowledge search and technology specialization, expands the research scope of key core technology breakthroughs at the micro level, and provides theoretical guidance and decision-making reference for enterprises to promote key core technology breakthroughs.