Background: Cancer incidence rates are increasing particularly in developing countries. It is crucial for policy makers to know basic cancer epidemiology in each region to design comprehensive prevention plans. There have hitherto been no population-based data available for cancer in Khuzestan province. The present report is a first from the regional population-based cancer registry for the period of 2002-2009. Materials and Methods: Data were collected retrospectively reviewing all new cancer patients whom were registered in Khuzestan province cancer registry during an 8-year period (2002-2009). All cases were coded based on the ICD-O-3 coding system and collected data were computerized using SPSS (Chicago, IL) software, version 11.5. The age standardized incidence rates (ASRs) per 100,000 person-year for all cancers were computed using the indirect method of standardization to the world population. Results: During the 8-year study period, 16,801 new cancer cases were registered. Based on the computed ASRs, the five most frequent malignancies in females were breast (26.4 per 100,000), skin (13.6), colorectal (5.72), stomach (4.31) and bladder(4.07) and in males, the five most frequent were skin (16.0 per 100,000), bladder (10.7),prostate (7.64), stomach (7.17), and colorectal (6.32).The ASR for all malignancies in women was 92.5 per 100,000, and that for men was 87.4. Conclusions: The observed patterns from the analysis of Khuzestan cancer registry data will lead to better understanding of the epidemiology of various malignancies in this part ofthe country and consequently provide a useful guide for authorities to make efficacious decisions and policies about a cancer control program for south-west Iran.