The aim of the research is to assess the effectiveness of Virtual Lab (experimental group) compared to Physical Lab (control group) in the level of Science Process Skill mastery of topic salt experiment. This research also was done to compare the students’ level of Science Process Skill mastery by gender and to find interaction effect between groups and gender on the level of Science Process Skill mastery. The instrument that used to evaluate the effectiveness is “Science Process Skill mastery test (SPST)”. A quasi-experimental research design with nonequivalent control group pre-test and post-test was used in this research. The participants of this research were chosen by purposive sampling from Malaysian 4th grade science stream students. This research involved a total of 147 participants, which is 64 male and 83 female. The two-way ANCOVA analysis showed that the effectiveness of group (VLab and PLab) on the mean score of SPST post-test was significant. The SPST post-test mean score of PLab is higher than the post-test mean score of Virtual Lab. It concluded that the students’ level of Science Process Skill mastery in experiments for confirmatory tests for anions and cations is better when Physical Lab is used. The effectiveness of gender on the mean score of SPST was not significant. The analysis also showed that the interaction effectiveness between group and gender in SPST was not significant. This means the group's influence on the mean score of SPST is not caused by the gender as well as the gender influence on the mean score of SPST is not caused by groups.