China has recently experienced a marked increase in the incidence of hand, foot and mouth disease (HFMD). Effective spatio-temporal monitoring of HFMD incidence is important for successful implementation of control and prevention measures. This study monitored county-level HFMD reported incidence rates for Sichuan province, China by examining spatio-temporal patterns. County-level data on HFMD daily cases between January 2008 and December 2013 were obtained from the China Information System for Disease Control and Prevention. We first conducted purely temporal and purely spatial descriptive analyses to characterize the distribution patterns of HFMD. Then, the global Moran's I statistic and space–time scan statistic were used to detect the spatial autocorrelation and identify the high-risk clusters in each year, respectively. A total of 212267 HFMD cases were reported in Sichuan province during the study period (annual average incidence 43·65/100000), and the incidence seasonal peak was between April and July. Relatively high incidence rates appeared in the northeastern–southwestern belt. HFMD had positive spatial autocorrelation at the county level with global Moran's I increasing from 0·27 to 0·52 (P < 0·001). Spatio-temporal cluster analysis detected six most-likely clusters and several secondary clusters from 2008 to 2013. The centres of the six most-likely clusters were all located in the provincial capital city Chengdu. Chengdu and its neighbouring cities had always been spatio-temporal clusters, which indicated the need for further intensive space–time surveillance. Allocating more resources to these areas at suitable times might help to reduce HFMD incidence more effectively.