Objective To investigate the effect of Early Intervention Denver Model (Early Start Denver Model, ESDM) on children with autism spectrum disorder(ASD). Methods From May 2017 to April 2018, forty four children aged 2-5 years with ASD were enrolled in the study and were randomly divided into the experimental group(n=20) and the control group (n=20). The experimental group received ESDM rehabilitation intervention and the control group received conventional rehabilitation intervention. Before and 6 months after intervention, all children were assessed by the Psycho-educational Profile-3rd Edition (PEP-3). Results After 6 months of intervention, the developmental age of cognition (30 (26, 34), 33(30, 44); Z=-3.728, P<0.001), imitation (33(29, 40), 38(32, 43); Z=-2.010, P=0.044), expression language (29(23, 39), 41(33, 50); Z=-3.923, P<0.01), receptive language (25(20, 32), 34(28, 38); Z=-3.727, P<0.01) and fine motor (29(23, 41), 39(33, 47) ; Z=-2.704, P=0.007) of the control group were significantly higher than those before intervention. In the experimental group, the developmental age of cognition (25(21, 32), 37(32, 40); Z=-3.922, P<0.01), imitation(22(17, 35), 39(38, 42); Z=-3.826, P<0.01), expression language (30(24, 35), 47(37, 53); Z=-3.824, P<0.01), receptive language (22(15, 32), 37(30, 43); Z=-3.924, P<0.01), fine motor (25(22, 33), 43(30, 52); Z=-3.924, P<0.01)and gross motor (24(17, 38), 40(27, 43); Z=-3.523, P<0.01)were significantly higher than those before intervention. Compared with the control group, the experimental group had significantly greater changes in the five regions: cognition(6(3, 10), 11(10, 20); Z=-2.821, P=0.005), expression language(6(4, 9), 12(7, 18); Z=-3.278, P=0.001), receptive language(5(3, 10), 12(7, 18); Z=-3.299, P=0.001), fine motor (7(1, 10), 13(10, 22); Z=-3.038, P=0.002)and gross motor(1(0, 10), 11(5, 16); Z=-2.568, P=0.01) of PEP-3 after intervention. Conclusion Both conventional intervention and ESDM intervention can improve the cognitive, expression language, receptive language, imitation and fine motor ability of children with ASD aged from 2 to 5 years, but ESDM intervention is more effective on improving the cognitive, language, imitation and fine motor ability of children with ASD. Key words: Early start Denver model; Autism spectrum disorder; Behavioral intervention; Child