In a letter to Victorian Liberal Party president Greg Mirabella seen by AAP, Senator Van said he could not remain a member of a party that "tramples upon the very premise on which our justice system is predicated".
It follows uproar over bombshell allegations against the senator by Independent senator Lidia Thorpe and former Liberal senator Amanda Stoker this week.
They both alleged Senator Van touched them inappropriately in previous years, which he has denied.
On Friday, Opposition Leader Peter Dutton confirmed further allegations have been brought against Senator Van and called on him to quit parliament.
"Given the Liberal Party's wholesale disregard for due process and natural justice in relation to allegations made against me, I write to resign my membership effective immediately," Senator Van said in the resignation letter.
"I cannot remain a member of a party that tramples upon the very premise on which our justice system is predicated.
"This is a travesty of justice and I reiterate that I deny the allegations made against me.
"I resign also acknowledging the cruel irony of doing so amidst public discourse about the weaponisation of allegations and the role of the rule of law which has at its centre the presumption of innocence."
Senator Van said he was "deeply distressed and hurt" and had been denied "procedural fairness".
He thanked colleagues, friends and family who had shown him support.
"I am grateful for their belief in my honesty and integrity," he said.
"I have worked tirelessly for the party and fought hard for its beliefs over many years."
Senator Van said he would continue to fight for "what I thought were the party's values - just not under its banner".
Senator Van has been under pressure to resign from parliament in the wake of the misconduct allegations, which he has strongly denied.
Independent senator Lidia Thorpe on Wednesday, under parliamentary privilege, accused Senator Van of harassment and sexual assault.
The following day, former Liberal senator Amanda Stoker accused Senator Van of inappropriately touching her in 2020.
Senator Van has said he has no recollection of the incident and he would never have acted inappropriately towards his then-colleague.
Mr Dutton expelled Senator Van from sitting in the Liberal party room in Canberra in the wake of the allegations.
On Friday, the Liberal Party took action to suspend all organisational resources and support from the Senator Van.
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