Nasopharyngeal carcinoma (NPC) is an uncommon disease in most countries but occurs with much greater frequency in southern China. This study aimed to examine the secular trends of NPC in urban Guangzhou over the time period of 2000-2011 using data from the Guangzhou Cancer Registry. Age-adjusted annual incidence rates of NPC were calculated by the direct method using the WHO World Standard Population (1960) as the reference. The average annual percentage change (AAPC) was used as an estimate of the trend. A total of 7,532 new cases of NPC and 3,449 related deaths were registered. In both genders, the peak incidence occurred in the 50- to 59-year age group, and this age distribution pattern remained similar throughout. The AAPC in NPC incidence rates was -3.26% (95% CI: -5.4%--1.1) for males and -5.74% (95% CI: -8.9%--2.5) for females, resulting in a total decrease of 39.3% (from 22.14 to 13.44 per 100,000 population) for males and 48.6% (from 10.1 to 5.18 per 100,000 population) for females over this 12-year period. The AAPCs in NPC mortality rates were -4.62% (95%CI: -3.5%--5.7) for males and -6.75% (95% CI: -5.2%--8.3) for females, resulting in a total decrease of -46.1% (from 12.1 to 6.54 per 100,000 population) for males and 51.7% (from 4.14 to 2.00 per 100,000 population) for females. The age-adjusted incidence and mortality rates of NPC declined during 2000-2011 in urban Guangzhou but remained high. Future efforts to improve prevention, early detection and treatment strategies are needed.