US District Judge Katherine Forrest concluded prosecutors could introduce evidence about six murder plots into Ross William Ulbricht's trial.
Formal jury selection starts on Tuesday.
Prosecutors say Ulbricht ran an underground website known as Silk Road, where hundreds of kilograms of cocaine, heroin and other drugs were sold to over 100,000 customers.
Ulbricht, who hid behind the pseudonym Dread Pirate Roberts, has pleaded not guilty.
"The charges in this case are extremely serious: Ulbricht is charged not with participating in a run-of-the-mill drug distribution conspiracy, but with designing and operating an online criminal enterprise of enormous scope, worldwide reach, and capacity to generate tens of millions of dollars in commissions," the judge has written.
"Evidence that defendant sought to protect this sprawling enterprise by soliciting murders-for-hire is, in this overall context, not unduly prejudicial."
Ulbricht was arrested October 1, 2013, at a San Francisco library, where he was swarmed by FBI agents who seized his computer.
The government says he started Silk Road in early 2011, saying he wanted to "create a website where people could buy anything anonymously, with no trail whatsoever that could lead back to them".
It said a spreadsheet found on his computer listed "sr inc" as an asset worth $104 million.
He was charged in Manhattan with conspiring to commit narcotics trafficking, conspiring to commit computer hacking and conspiring to commit money laundering for a scheme that the government said stretched from January 2011 through September 2013.
He is also charged in federal court in Baltimore. If convicted in both cases, he could face up to life in prison.
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