Objective: Keloid patients usually have local pruritus and pain. In our clinical work, we have found keloid patients after receiving hyperbaric oxygen (HBO) therapy reflect less pruritus and pain. The hypothesis was that patients with keloid and a history of HBO therapy would have less pruritus and pain than patients without HBO therapy, and the pruritus or pain-related factors were detected in keloid with/without HBO therapy and normal skin. Methods: Three groups of samples were established: keloid samples from patients with HBO therapy for two weeks before and after surgery (H group); keloid samples from patients without HBO therapy (G group); normal skin samples from patients without obvious scar (N group). Hematoxylin and eosin (H&E) staining was used to observe morphological changes. Pruritus/pain related factors: Tryptophan Hydroxylase1 (TPH1), connexin-43 (Cx43) and transient receptor potential vanilloid type 1 (TRPV1) were detected by immunofluorescence and western blot technology. The expression of these factors’ mRNA was also measured by the real-time quantitative polymerase chain reaction (RT-qPCR). Results: Among three groups, G group presented significantly highest expression levels of TPH1, Cx43 and TRPV1, conversely, N group presented significantly lowest expression levels of TPH1, Cx43 and TRPV1. Conclusion: TPH1, Cx43 and TRPV1 were overexpressed in the samples of keloid patients, indicating that the pruritus and pain of keloid might be related to these factors. Furthermore, TPH1, Cx43 and TRPV1 were expressed highest in keloid patients without HBO therapy, indicating that HBO therapy might relief pruritus of keloid patients by regulating these factors.