The two-time winner wrote to his former Astana team-mate in an open letter explaining that he believes Aru still has the possibility to race when the Giro starts from his home island on May 5.
Aru hurt his knee in a training crash and subsequently cancelled his Giro plans.
"Fabio, don't lose hope. Not yet," Nibali wrote in La Gazzetta dello Sport newspaper on Wednesday.
Aru already helped Nibali, who now races with Bahrain-Merida, win and placed second and third in the Giro d'Italia. He won the 2015 Vuelta a España by overthrowing Tom Dumoulin.
"Although it is very difficult, perhaps impossible, I still think there is a chance to see you at the start of the Giro in Alghero. You and I are two reference points in Italian cycling for the Grand Tours, and with your absence in Sardinia, we'd all lose.
"In my heart, I hope that something will happen at the end of these days off that the doctor recommended to you."
Aru fell on the roads in Sierra Nevada, Spain, at an altitude camp a week ago on Sunday. He posted on Twitter a photo of his swollen left knee over the weekend and his Astana team released details of the incident shortly after.
"[My coach] thought I'd fractured my pelvis," Aru said. "But I only have some scratches, and nothing on the hands. The cartilage of the knee is inflamed and compressed. I fell heavily and the cartilage absorbed the impact."
The team said that Aru needs to stop riding for 10 days while the knee heals, which means he misses important training and racing days ahead of the Giro d'Italia start. He was due to race the Tour of the Alps (Trentino) and the Tour de Romandie.
"Fabio, I'm not a doctor and attention to your knee should come first," Nibali continued. "At times, when doctors recommend a certain number of days off, we can anticipate it. Maybe in a few days the situation will change slightly for the better. Fabio, don't give up even if it all seems lost.
"Everyone knows what happened and no one is asking that you are 100 per cent at the start. You could try and if you see it's impossible, leave the race. Or maybe things may improve and you can stay with your form improving, taking revenge in the third week. But apart from this, the Giro allow you to put in some important work for the Tour de France. And for the future."
Aru was one of a long list of favourites, and one of the top Italians with Nibali, for the 100th Giro d'Italia.
Nibali (team Bahrain-Merida) will race along with Sky's Geraint Thomas and Mikel Landa, Adam and Simon Yates (Orica-Scott), Nairo Quintana (Movistar), Tom Dumoulin (Sunweb), Steven Kruijswijk (LottoNL-Jumbo), Thibaut Pinot (FDJ) and Bauke Mollema (Trek-Segafredo).
"I can look at this as an athlete, not as a fan or a sports director," added Nibali. "I know what it means to prepare months for a goal, and I know how special the Giro is for you given it pass your homeland. In particular for us because we are two islanders, and it doesn't happen often that the Giro visits."
The Giro starts with three stages in Sardinia. It last visited 10 years ago, in 2007. It continues with two stages in Sicily, with the fifth stage arriving to Nibali's hometown of Messina.
Without Aru, 2011 winner Michele Scarponi will lead Astana. Aru could race the Tour de France or the Vuelta a España later in 2017 if he does miss the Giro.
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