Objective. The physiological sensation of pain and rapid response to stimuli serve as an adaptive way to avoid harmful situations. Our purpose was to investigate why this protection disappears or almost disappears for patients with congenital indifference to pain (CIP). Design. The study was designed as a case report by scanning the candidate genes within CIP patients. Setting. The study was set at the Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Patients. We reported patients from two Chinese families that showed insensitivity to pain and were diagnosed with CIP by a neurologist. Different from recently reported studies, our patients were not entirely painless, but demonstrated little pain sensation from injuries. Measures. The measures made were novel mutations within SCN9A. Results. Sequence analysis of candidate genes of two affected individuals identified two novel heterozygous mutations (M899I and M932L) in the SCN9A gene. Furthermore, a novel nonsynonymous single-nucleotide polymorphism (SNP) within the SCN9A gene was revealed in affected proband and several unaffected family members. This polymorphism (c. 3312G& T, which produces the amino acid substitution V1104L in human Nav1.7), is present in 6.5% of healthy Chinese. Conclusions. We speculate that the mutations may be the cause of partial deletion of pain perceptionin in our probands, and the novel polymorphism V1104L may have a predictive role in the pain sensation of healthy individuals.