To solve the problem that there are a lot of invalid mutations, and the performance is wasted in Coverage-Guided Fuzzing (CGF), an adaptive sensitive region mutation algorithm was proposed. Firstly, the mutation locations were divided into effective mutation location set and invalid mutation location set according to whether the mutated test case executed a new path. Then, the sensitive region was determined based on the effective mutation location, and the subsequent mutations were concentrated in the sensitive region. In the subsequent fuzzing process, the sensitive region of the corresponding seed was adjusted adaptively according to the execution results of test cases, so as to reduce the invalid mutations. In addition, a new seed selection strategy was designed to assist the sensitive region mutation algorithm. The adaptive sensitive region mutation algorithm was integrated into the American Fuzzy Lop (AFL) to form Sensitive-region-based Mutation American Fuzzy Lop (SMAFL). SMAFL was evaluated on 12 popular applications and the experimental results showed that compared to AFL,when there was one initial seed, SMAFL found 31.4% more paths on average, increased the number of fuzzed counts by 3.4 times, and achieved higher code coverage across all 12 programs. In the testing of the LAVA-M dataset, SMAFL found 2 more bugs than AFL, and found the same bugs in a shorter time. Overall, the adaptive sensitive region mutation algorithm can improve the exploration efficiency of fuzzers.