Abstract: Objective To acquaint the occurrence, post-exposure prophylaxis (PEP) and prognostic follow-up of occupational exposure to HIV from 2010 to 2015 in Dehong Prefecture in Yunnan Province, so as to provide reference for carrying out and tightening the protection work of occupational exposure to HIV. Methods The CDC of Dehong Prefecture collected total occupational HIV exposure cases from 2004 to 2015, which then were put into pooling and statistical analysis. Results From 2010 to 2015, a total of 323 cases of occupational HIV exposure occurred and none suffered HIV infection, of whom 220 (68.11%) were females, of whom 229 (70.90%) were less than 35 years old, and of whom 209 (64.71%) were health care workers. needle or other sharp instrument sticking occupied the most proportion of 72.14% (233/323). Medical facilities were the main areas where the occupational HIV exposure occurred (82.66%, 267/323). After exposure to HIV, total 323 immediately washed or disinfected skin or mucous membranes whereas 279 had received post-exposure prophylaxis(PEP), 156 of 279 completed the 28-day course. The cases of occupational HIV exposure differed largely. Conclusions Insisting on the principle of universal protection, employing timely and emergent treatment and PEP after exposure assessment are helpful for avoiding and reducing HIV infection due to occupational exposure.