This study was conducted to determine the effectiveness of virtual laboratory based on semi second life (s-SL) on higher order thinking skills of general senior secondary school in chemistry learning process. The research design was adopted posttest only design approach to a quasi-experimental. This study was conducted in the one of public general senior secondary school in 3T regions -- Bangkalan City -- one of the cities in East Java Province, Indonesia. There were 81 students in the grade 11 of natural science who involved in this study. The participants were divided into three groups, namely the students who did practical work by demonstration methods in chemistry real laboratory, the students who did practical work by experiment methods in virtual laboratory based on s-SL, and the students who did practical work by combination both of them (demonstration methods in chemistry real laboratory and experiment methods in virtual laboratory based on s-SL). The students in each group was tested by posttest of higher order thinking skills. The data was analysed with one-way ANOVA. The results of data analysis shows that there is a significance difference of each groups. Virtual laboratory based on s-SL has enough effect on the students' higher order thinking skills.